scholarly journals Epithelial cell migration as a potential therapeutic target in early lung cancer

2017 ◽  
Vol 26 (143) ◽  
pp. 160069 ◽  
Author(s):  
Fraser R. Millar ◽  
Sam M. Janes ◽  
Adam Giangreco
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Rho Gtpase ◽  
Early Stage ◽  
Cancer Type ◽  
Preclinical Research ◽  
Early Stage Lung Cancer ◽  
Early Stage Disease ◽  
Early Lung Cancer ◽  
Stage Disease

Lung cancer is the most lethal cancer type worldwide, with the majority of patients presenting with advanced stage disease. Targeting early stage disease pathogenesis would allow dramatic improvements in lung cancer patient survival. Recently, cell migration has been shown to be an integral process in early lung cancer ontogeny, with preinvasive lung cancer cells shown to migrate across normal epithelium prior to developing into invasive disease. TP53 mutations are the most abundant mutations in human nonsmall cell lung cancers and have been shown to increase cell migrationviaregulation of Rho-GTPase protein activity. In this review, we explore the possibility of targeting TP53-mediated Rho-GTPase activity in early lung cancer and the opportunities for translating this preclinical research into effective therapies for early stage lung cancer patients.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals Implementation of targeted screening for lung cancer in a high-risk population within routine NHS practice using low-dose computed tomography

Thorax ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 348-350 ◽  
Author(s):  
Helen Grover ◽  
Thomas Ross ◽  
Elizabeth Fuller
Keyword(s):  
Lung Cancer ◽  
Low Dose ◽  
Screening Programme ◽  
Early Stage ◽  
High Risk Population ◽  
Curative Intent ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Targeted Screening ◽  
Low Dose Computed Tomography

We report a primary care-based lung cancer targeted screening programme using low-dose CT (LDCT) in South Tyneside and Sunderland. Ever smokers with ≥10 pack-years aged 55–74 years were identified at annual COPD review. 925 individuals attended for LDCT. 2% (n=19/925) had lung cancer diagnosed. 66.7% (n=14/21) had early stage disease and 78.9% (n=15/19) were offered treatment with curative intent. 79.3% of individuals attending for LDCT were ranked in the lowest deprivation quintiles. This approach has been successfully established in routine NHS practice; it is effective with improvements in stage of disease and engages individuals in deprived areas.

One-year survival and physical functioning with surgery compared to no surgery in early-stage lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6584-6584
Author(s):  
Paul R. Walker ◽  
Sam Cykert ◽  
Franklin McGuire ◽  
Lloyd Edwards ◽  
Peggye Dilworth-Anderson
Keyword(s):  
Lung Cancer ◽  
Functional Status ◽  
Physical Functioning ◽  
Early Stage ◽  
Short Form ◽  
Early Stage Lung Cancer ◽  
Early Lung Cancer ◽  
One Year ◽  
Surgical Group ◽  
Stage Lung Cancer

6584 Background: Medical co-morbidities in patients with lung cancer frequently impact a treatment decision out of fear of doing harm without a benefit. A prospective study looking at racial disparity factors associated with surgery decisions in early lung cancer identified > 2 co-morbidities with an Odds Ratio (OR) of 0.04 of going to surgery for African Americans (AA) patients, yet a 10-fold higher likelihood of Caucasians (C) going to surgery with an OR 0.45. (Cykert et al JAMA 2010: 303: 2368). Methods: 386 out of the original437 patients with early stage lung cancer and no absolute contraindications to surgery were evaluated at multiple institutions for relative co-morbidities and with an initial Short Form 12 (SF-12) to assess physical functional status at enrollment and one year after enrollment. One year mortality and physical functional status was assessed. Results: 66% of C underwent surgery compared to 55% of AA (p = .048). One year mortality was not different between the AA (15%) and C (15.4%) populations (p=0.9); however not powered for a survival difference between surgery and no surgery. One year mortality in the overall surgical group was 10.8% compared to 22.8% in the non-surgical group; OR 0.50 (p<0.001). Patients with > 2 co-morbidities at diagnosis had a 27.5% one year mortality compared to 13.5% with < 2 co-morbidities; OR 1.7 (p=0.01). Combined analysis of co-morbidities and surgery revealed those with < 2 co-morbidities having surgery experienced a 10% one year mortality and those with > 2 co-morbidities 19%; without surgery one year mortality was 20% and 31% respectively. Despite > 2 co-morbidities, there was a 12% absolute mortality reduction with surgery. Regression analysis controlling for age and co-morbidities identified no physical functioning decline with surgery compared to the non-surgical group. Conclusions: One year mortality was doubled in patients with early lung cancer who declined surgery compared to those treated with surgery. There was no increased physical functioning decline in patients treated with surgery compared to no surgery. Treatment decisions in early lung cancer should be based on the survival benefit and not a perceived concern of physical functioning decline.

Clinical and molecular characteristics of non-small cell lung cancer patients from rural Maine.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18237-e18237
Author(s):  
Antoine Harb ◽  
Adam Curtis ◽  
Laura Skacel ◽  
Michael Babcock ◽  
Marek Skacel
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
P53 Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Disease Free

e18237 Background: Non-Small Cell Lung Cancer (NSCLC) is the most common malignancy worldwide and the leading cause of malignancy-related mortality in the United States. The state of Maine in particular, has one of the highest rates of lung cancer in the country. Methods: We reviewed all NSCLC patients (adenocarcinoma (AC) and squamous cell (SC) histology) diagnosed between January 2017 and June 2018 at Northern Light Cancer Institute. 261 patients with clinical follow-up were identified. We correlated their clinical characteristics with molecular abnormalities identified by Next Generation Sequencing (NGS) and Fluorescence in situ hybridization, PD-L1 status by immunohistochemistry, disease-free and overall survival. Results: 210 patients had AC and 51 SC. They were evenly split between men and women. The median age at diagnosis was 68 years. 99% of patients were Caucasian. 15 patients were never smokers, the rest were equally divided between active and previous smokers. 44% had early stage disease (I/II) and 56% had late stage disease (III/IV) on presentation. 36.4% had a PD-L1 high status. The frequencies of the molecular aberrations identified in AC and SC are listed in the table below: Treatment differed by stage, including surgery/Radiation +/- adjuvant chemotherapy for early stage disease, definitive chemo-radiation followed by immunotherapy for stage III disease. Stage IV patients were treated with immunotherapy, combination chemo-immunotherapy, targeted therapy, palliative radiation and hospice referral. After a median follow-up of 10.6 months, overall survival (OS) was 66%. Disease free survival (DFS) was 33%. Using univariate (chi-square), multivariate (logistic regression) and Kaplan-Meier (log rank) analyses, we identified that in addition to a high clinical stage, which was associated with shorter OS and DFS, high PD-L1 status, and the presence of p53 mutation, were independent predictors of shorter OS, and p53 mutation of shorter DFS. Conclusions: NGS-based molecular testing deployed in real-time non-academic setting proved to be a valuable tool to identify therapeutic and prognostic targets in NSCLC. Besides those endorsed by the NCCN guidelines, p53 mutation is a common abnormality associated with adverse outcomes. While high PD-L1 expression is a desirable immunotherapy marker, its presence also predicted adverse overall outcomes in our patients.[Table: see text]

PD-1 Blockade in Early-Stage Lung Cancer

2019 ◽  
Vol 70 (1) ◽  
pp. 425-435 ◽  
Author(s):  
Samuel Rosner ◽  
Joshua E. Reuss ◽  
Patrick M. Forde
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Immune Checkpoint Blockade ◽  
Advanced Lung Cancer ◽  
Early Stage Lung Cancer ◽  
Early Results ◽  
Stage Disease ◽  
Relapse Rates ◽  
Stage Lung Cancer

Early-stage non–small cell lung cancer is a potentially curable disease, but with relapse rates exceeding 50% with standard treatments, this is a patient population in critical need of therapy innovation. Immunotherapy with immune checkpoint blockade has revolutionized the treatment strategy for advanced lung cancer. However, the role of this therapy in earlier-stage disease is largely unknown. The study of immunotherapy in earlier-stage disease has many advantages, including assessment of pathologic response and incorporation of translational scientific analyses to evaluate antitumor immune responses. Multiple clinical trials are currently under way, with promising early results.

scholarly journals Longitudinal Changes in Depression Symptoms and Survival Among Patients With Lung Cancer: A National Cohort Assessment

2016 ◽  
Vol 34 (33) ◽  
pp. 3984-3991 ◽  
Author(s):  
Donald R. Sullivan ◽  
Christopher W. Forsberg ◽  
Linda Ganzini ◽  
David H. Au ◽  
Michael K. Gould ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Depression Symptoms ◽  
Depression Symptom ◽  
Early Stage Disease ◽  
Longitudinal Changes ◽  
Stage Disease ◽  
Symptom Remission ◽  
New Onset

Purpose Depression symptoms are common among patients with lung cancer; however, longitudinal changes and their impact on survival are understudied. Methods This was a prospective, observational study from the Cancer Care Outcomes Research and Surveillance Consortium from five US geographically defined regions from September 2003 through December 2005. Patients enrolled within 3 months of their lung cancer diagnosis were eligible. The eight-item Center for Epidemiologic Studies Depression scale was administered at diagnosis and 12 months’ follow-up. The main outcome was survival, which was evaluated using Kaplan-Meyer curves and adjusted Cox proportional hazards modeling. Results Among 1,790 participants, 681 (38%) had depression symptoms at baseline and an additional 105 (14%) developed new-onset depression symptoms during treatment. At baseline, depression symptoms were associated with increased mortality (hazard ratio [HR], 1.17; 95% CI, 1.03 to 1.32; P = .01). Participants were classified into the following four groups based on longitudinal changes in depression symptoms from baseline to follow-up: never depression symptoms (n = 640), new-onset depression symptoms (n = 105), depression symptom remission (n = 156), and persistent depression symptoms (n = 254) and HRs were calculated. Using the never-depression symptoms group as a reference group, HRs were as follows: new-onset depression symptoms, 1.50 (95% CI, 1.12 to 2.01; P = .006); depression symptom remission, 1.02 (95% CI, 0.79 to 1.31; P = .89), and persistent depression symptoms, 1.42 (95% CI, 1.15 to 1.75; P = .001). At baseline, depression symptoms were associated with increased mortality among participants with early-stage disease (stages I and II; HR, 1.61; 95% CI, 1.26 to 2.04), but not late-stage disease (stages III and IV; HR, 1.05; 95% CI, 0.91 to 1.22). At follow-up, depression symptoms were associated with increased mortality among participants with early-stage disease (HR, 1.71; 95% CI, 1.27 to 2.31) and those with late-stage disease (HR, 1.32; 95% CI, 1.04 to 1.69). Conclusion Among patients with lung cancer, longitudinal changes in depression symptoms are associated with differences in mortality, particularly among patients with early-stage disease. Symptom remission is associated with a similar mortality rate as never having had depression.

scholarly journals Management and outcomes of patients with chronic obstructive lung disease and lung cancer in a public healthcare system

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251886
Author(s):  
John R. Goffin ◽  
Sophie Corriveau ◽  
Grace H. Tang ◽  
Gregory R. Pond
Keyword(s):  
Lung Cancer ◽  
Respiratory Infections ◽  
Early Stage ◽  
Multivariable Analysis ◽  
Chronic Obstructive Lung Disease ◽  
Stage I ◽  
Public Healthcare ◽  
Chronic Obstructive ◽  
Early Stage Disease ◽  
Stage Disease

Hypothesis There is limited data on the care and outcomes of individuals with both chronic obstructive pulmonary disease (COPD) and lung cancer, particularly in advanced disease. We hypothesized such patients would receive less cancer treatment and have worse outcomes. Methods We analyzed administrative data from the province of Ontario including demographics, hospitalization records, physician billings, cancer diagnosis, and treatments. COPD was defined using the ICES-derived COPD cohort (1996–2014) with data from 2002 to 2014. Descriptive statistics and multivariable analyses were undertaken. Results Of 105 304 individuals with lung cancer, 43 375 (41%) had stage data and 36 738 (34.9%) had COPD. Those with COPD were likely to be younger, have a Charlson score ≤ 1, have lower income, to live rurally, and to have stage I/II lung cancer (29.8 vs 26.5%; all p<0.001). For the COPD population with stage I/II cancer, surgery and adjuvant chemotherapy were less likely (56.8 vs. 65.9% and 15.4 vs. 17.1%, respectively), while radiation was more likely (26.0 vs. 21.8%) (p all < 0.001). In the stage III/IV population, individuals with COPD received less chemotherapy (55.9 vs 64.4%) or radiation (42.5 vs 47.5%; all p<0.001). Inhaler and oxygen use was higher those with COPD, as were hospitalizations for respiratory infections and COPD exacerbations. On multivariable analysis, overall survival was worse among those with COPD (HR 1.20, 95% CI 1.19–1.22). Conclusions A co-diagnosis of COPD and lung cancer is associated with less curative treatment in early stage disease, less palliative treatment in late stage disease, and poorer outcomes.

scholarly journals EU Policy on Lung Cancer CT Screening 2017

2017 ◽  
Vol 2 (Suppl. 1) ◽  
pp. 1-8 ◽  
Author(s):  
John K. Field ◽  
Javier Zulueta ◽  
Giulia Veronesi ◽  
Matthijs Oudkerk ◽  
David R. Baldwin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Early Stage ◽  
Lung Cancer Screening ◽  
Expert Group ◽  
Early Stage Disease ◽  
Ct Screening ◽  
Stage Disease ◽  
Eu Commission ◽  
The Eu

Background: Lung cancer kills more Europeans than any other cancer. In 2013, 269,000 citizens of the EU-28 died from this disease. Lung cancer CT screening has the potential to detect lung cancer at an early stage and improve mortality. All of the randomised controlled trials and cohort low-dose CT (LDCT) screening trials across the world have identified very early stage disease (∼70%); the majority of these LDCT trial patients were suitable for surgical interventions and had a good clinical outcome. The 10-year survival in CT screen-detected cancer was shown to be even higher than the 5-year survival for early stage disease in clinical practice at 88%. Methods: Setting up of an EU Commission expert group can be done under Article 168(2) of the Treaty on the Functioning of the European Union, to develop policy and recommendation for Lung cancer CT screening. The Expert Group would undertake: (a) assist the Commission in the drawing up policy documents, including guidelines and recommendations; (b) advise the Commission in the implementation of Union actions on screening and suggest improvements to the measures taken; (c) advise the Commission in the monitoring, evaluation and dissemination of the results of measures taken at Union and national level. Results: This EU Expert Group on lung cancer screening should be set up by the EU Commission to support the implementation and suggest recommendations for the lung cancer screening policy by 2019/2020. Conclusion: Reduce lung cancer in Europe by undertaking a well-organised lung cancer CT screening programme.

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