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S.M. Janes
Moderator of
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MINI 11 - Tobacco Control and Prevention (ID 108)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Prevention and Tobacco Control
- Presentations: 11
- Moderators:S.M. Janes, E. Stone, K.M. Cummings
- Coordinates: 9/07/2015, 16:45 - 18:15, 601+603
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MINI11.01 - The Upshot of Passive Smoke (ETS) Exposure on Pneumonia Risk in Children Under 7 Years in Nigeria (ID 517)
16:45 - 16:50 | Author(s): B. Obiazi-Odiase
- Abstract
- Presentation
Background:
This study considers pneumonia risk on children under age 7 in Northern Nigeria exposed to ETS. The numerous adverse effects of Environmental Tobacco Smoke (ETS) on the non-smoking public have being evidenced through decades of research. This does not only affect adults but children. ETS effects on children have shown to be grave as it worsens asthma conditions, increases pneumonia cases and causes Sudden Infant Death Syndrome (SIDS).
Methods:
Most residents in all 44 Local Government Areas (LGAs) in Kano State of Northern Nigeria took part in a population-based large-scale cross-sectional survey in Kano state from 2007-2010. Demographic information coupled with socioeconomic status, smoking status and house environment of each household member, was collected from participants. Pneumonia case reported among children aged 7 years and below in each household in the previous 18 months were recorded based on parent’s/guardian's report.
Results:
Out of a total of 528, 800 people resident in 102,334 homes indentified in the survey areas and visible/present as at the time of the study, 52,888 (10%) were children aged 7 years and below. While the prevalence of ETS exposure on children was 81%, the prevalence of reported pneumonia cases was 3.5%. Multiple logistic regression analysis showed that exposure to ETS was independently associated with reports of pneumonia cases (adjusted odds ratio 1.55, 95% CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than women (63.5% vs 44.1%). It is estimated that 32.7% of childhood pneumonia in the northern region of Nigeria is attributable to ETS.
Conclusion:
Attention should be given to reduction to children’s exposure to ETS not only in Nigeria but in all affected areas mostly all parts of the world. If nothing is done to protect children, there will be millions of avoidable deaths attributable to Pneumonia heightened by ETS exposure. This is a case of concern for any one involved in lung cancer/tobacco control.
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MINI11.02 - Frizzled9 as a Predictor of Response to Iloprost Chemoprevention of Lung Cancer (ID 2397)
16:50 - 16:55 | Author(s): D.T. Merrick, M. Tennis, L. Nield, R.L. Keith
- Abstract
- Presentation
Background:
Lung cancer remains the leading cause of cancer death in the United States and chemoprevention offers an appealing area of investigation in the face of limited therapeutic success. Improvement in endobronchial histology was recently demonstrated in former smokers after oral iloprost treatment. Of the 48 patients who received iloprost in the chemoprevention trial, 23 had regressive histology and 25 had stable or progressive histology. Identifying markers that predict which patients will respond to treatment will help refine target populations for future trials and clinical applications. In vitro studies of NSCLC indicate that iloprost, a prostacyclin analogue, acts through the G-protein coupled receptor Frizzled 9 (Fzd9) instead of the prostacyclin receptor. We hypothesize that Fzd9 expression status predicts response to iloprost chemoprevention and that current smokers may not respond to iloprost treatment due to carcinogen-induced decreases in Fzd9 expression. Prostacyclin may also induce expression of Fzd9, leading to increased anti-tumor signaling.
Methods:
Fzd9 expression was measured by quantitative real-time PCR in RNA extracted from mouse and human tissues, cultured dysplastic cell lines, and cultured human bronchial epithelial cells (HBEC). In the urethane model, FVB wild type and transgenic mice were exposed to a single dose of urethane and sacrificed after 20 weeks. In the smoking model, FVB wild type and transgenic mice were sacrificed after one week of cigarette smoke exposure. Human matched tumor and normal tissue and dysplastic cell lines were acquired from the University of Colorado SPORE in Lung Cancer Tissue Bank. HBEC were exposed to 5ug/ml cigarette smoke condensate and 10uM iloprost in culture media.
Results:
Human lung tumors demonstrated reduced Fzd9 mRNA expression compared to matched normal lung tissue. Fzd9 expression is also decreased in human primary dysplastic cell lines, suggesting that loss of Fzd9 expression occurs early in early lung lesions. In a urethane mouse model of lung cancer, Fzd9 mRNA expression is reduced in lung tumors compared to matched, uninvolved lung tissue. Tumors from urethane exposed prostacyclin synthase overexpressing (PGIStg) mice have higher Fzd9 expression compared to tumors from wild type mice. In a one-week smoking model, Fzd9 expression is decreased in lung from wild type smoked mice but higher in PGIStg smoked mice. In HBEC exposed to cigarette smoke, Fzd9 expression decreases and remains low with continued exposure from 1 to 28 weeks. After two weeks of exposure to iloprost alone, HBEC cells demonstrated increased Fzd9 expression.
Conclusion:
These initial studies suggest that Fzd9 expression is lost lung epithelial cells with early smoking-induced damage. Fzd9 expression will be measured in baseline and follow up biopsy tissues from the iloprost clinical trial. This study has the potential to improve iloprost lung cancer chemoprevention by allowing future trials to more effectively target high-risk patients and by providing a clinical biomarker for identification of chemoprevention candidates.
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MINI11.04 - A New Preclinical Model of Airway Progenitor Cells to Identify Responders to Iloprost-Mediated Chemoprevention (ID 1698)
16:55 - 17:00 | Author(s): J.B. Kwon, I. Nakachi, R.L. Keith, D.T. Merrick, M. Edwards, S. Leach, W.A. Franklin, Y.E. Miller, M. Ghosh
- Abstract
- Presentation
Background:
Lung cancer is the leading cause of cancer related deaths worldwide. The 5-year survival rate for this cancer is only 16%. Chemoprevention can improve prognosis in these patients. However, previous attempts at lung cancer chemoprevention that were soley based on epidemiological data were ineffective. Squamous cell lung cancer develops through a series of bronchial lesions or dysplasia. Persistent dysplasia harbors similar genetic changes as the tumor and has significantly higher chance of progression. Thus, bronchial dysplasia is a risk biomarker for SCC and improvement in dysplasia grade can be used as an outcome for chemoprevention trials. The long-acting prostacyclin analogue, iloprost is the only drug that has improved dysplasia in former smokers (p = 0.006). Despite this positive outcome we have little insight into the mechanisms of iloprost function. Understanding these mechanisms would be essential to identify people who have the highest chance to benefit from iloprost treatment. We propose that this endeavor will require a preclinical model that recapitulates the human disease and is amenable to mechanistic studies.
Methods:
Airway progenitor cells are critical for the maintenance of normal airways, because of their ability to self-renew (i.e. replicate) and differentiate into all cell-types of the airway (i.e. multipotentiality). Together these properties allow progenitors to return injured tissue to normal structure and function. In dysplasia, normal bronchial epithelium is changed into one that contains increased numbers of basal cells and lacks ciliated cells. These findings led to our hypothesis that ‘airway progenitors are malfunctioning in dysplasia’. Previously we showed that Keratin (K) 5/p63-expressing basal cells are the multipotential progenitors of the airway epithelium. During in vitro culture these cells form a unique 3-deimensional structure called the rim clone, which allows them to be distinguished from non-progenitors. To investigate a role of epithelial progenitors in dysplasia, we have collected bronchial biopsies from high-risk smokers and purified rim clone forming basal progenitor cells.
Results:
We demonstrate that both self-renewal and multipotentiality of progenitors is significantly (p < 0.001 for both) decreased in dysplasia. During differentiation in vitro at the air-liquid interface, progenitors from normal biopsies generated a normal epithelium. In contrast, progenitors from dysplasia made a squamous epithelium containing only basal cells and lacking ciliated cells. Mutational analyses of paired samples from epithelial brushings and biopsy-derived progenitors identified the same somatic mutations in p53, Notch 1, Notch 3, Survivin and FGFR1. Thus, epithelial progenitor culture reflects the histologic and genetic changes of dysplasia and therefore can be used as a personalized, preclinical model. A proof of concept study where dysplastic progenitor cells were treated with iloprost resulted in decreased dysplasia in 2 out of 3 cases.
Conclusion:
Thus our data indicate that progenitor cell cultures from a patient’s dysplasia may be used to identify responders versus non-responders to iloprost, as well as other chemopreventives. Future studies could focus on identifying downstream mechanisms via which iloprost exerts its beneficial effect.
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MINI11.05 - Prevalence Use of Others Tobacco Products: Findings from the ITC Brazil Survey (ID 2769)
17:00 - 17:05 | Author(s): C.D.A. Perez, T.M. Cavalcante, F.L. Mendes
- Abstract
- Presentation
Background:
Tobacco use is responsible for 5.4 million deaths every year worldwide and a leading cause of preventable death. Brazil is widely regarded as an international leader in tobacco control. The WHO FCTC aims to protect individuals from the consequences of tobacco use by providing a framework for tobacco control measures. Parties are obligated to implement measures to prevent and reduce all tobacco consumption and to monitor the magnitude and patterns of tobacco use. The ITC Brazil Survey includes several measures to assess smokers’ tobacco use behaviour, such as cigarette consumption and types of products used.
Methods:
The International Tobacco Control Policy Evaluation Survey (ITC) Brazil Survey is a longitudinal cohort survey and was conducted in Brazil with 1,200 adult smokers and 600 adult non-smokers living in three cities. Telephone-administered surveys were conducted using an area stratified random sampling strategy, yielding a representative sample of the four largest cities in Brazil (Rio de Janeiro, Porto Alegre, and Sao Paulo). The Wave 1 Survey (in 2009) and Wave 2 (2012-2013) included questions a variety of tobacco control measures, including use of tobacco products.
Results:
Brazilian smokers in the ITC Survey smoked mainly factory-made cigarettes and five percent reported that they regularly smoke a flavored brand (including menthol). In Wave 2, all respondents were asked about their use of other tobacco products, and the results show evidence of other tobacco product use even among non-cigarette smokers. Thirteen percent of the overall sample (smokers and non-smokers combined) have smoked clove cigarettes, 10% have smoked cigars, 8% smoked shisha, 5% smoked pipes, and 4% smoked bidis. The percentage of smokers and non-smokers in the sample who have tried various tobacco products, by city, shows a significantly higher use of shisha among smokers in São Paulo (18%) compared to Rio de Janeiro (5%) and Porto Alegre (8%), and non-smokers in São Paulo were significantly more likely to smoke cigars than in the other two cities. Despite the prohibition of electronic cigarettes (e-cigarettes) sale, importation, and advertising in Brazil since August 2009, in the ITC Brazil Wave 2 Survey, respondents were asked “Have you ever heard of electronic cigarettes or e-cigarettes?”. The results showed that 35% of smokers and 29% of non-smokers had heard of them. The highest level of awareness of the product was in Porto Alegre where 39% of smokers and 29% of non-smokers had heard of them. Among smokers who had heard of e-cigarettes, 38 smokers (12%) and one non-smoker reported trying these products.
Conclusion:
Daily consumption of cigarettes is relatively high in Brazil for both male and female daily smokers, based on a comparison of the average number of cigarettes smoked per day among 20 ITC countries and an average consumption of 17 cigarettes per day — twice the average consumption of smokers in Mexico, so its recommended to reinforce educational campaigns about the dangers of smoking, and the electronic cigarette use, increase its inspections and mainly reinforce educational campaigns about the dangers of shisha.
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MINI11.06 - Comprehensive Tobacco Control Programs Reduce Tobacco Use and Secondhand Smoke Exposure: A Systematic Review (ID 3004)
17:05 - 17:10 | Author(s): J.A. Reynolds, Y. Peng, N. Vaidya, C.G. Dumitru, D.P. Hopkins
- Abstract
- Presentation
Background:
Tobacco use is the single greatest cause of preventable disease, disability, and death in the U.S. Over the last few decades, several states have implemented comprehensive tobacco control programs (CTCP) to reduce tobacco use and secondhand smoke (SHS) exposure. This Community Guide (CG) systematic review was conducted to examine CTCP effectiveness in reducing tobacco use and tobacco-related diseases and deaths.
Methods:
A systematic search was conducted (search period Jan 2000-July 2014) to identify and abstract qualifying studies using standard CG systematic review methods. Studies published prior to 2000 were identified from a previous Community Guide review and added. Summary measures were calculated when possible and narrative results were provided when effect estimates could not be pooled. The review team worked under the guidance of the Community Preventive Services Task Force (CPSTF), a non-federal, independent, volunteer body of public health and prevention experts.
Results:
The review team identified 60 eligible studies; only results from the U.S. studies are reported here (55 studies). Most of the U.S. studies evaluated CTCP at the state level (48 studies from 10 states) with the remaining studies at the city (3 studies) and local or community level (4 studies). States with a CTCP reduced tobacco use prevalence among adults by a median of 2.8 percentage points (pct pts) [Interquartile interval (IQI): -3.5 to -2.4 pct pts; 12 studies]; reduced tobacco use prevalence among young people by a median of 4.5 pct pts (IQI: -6.0 to -0.7 pct pts; 9 studies); reduced cigarette pack sales by a median of 12.7% (IQI: -20.8% to -5.5%; 7 studies); and reduced daily tobacco product consumption by a median of 17.1% (IQI: -43.4% to -13.5%; 6 studies). Narrative results showed that states with a CTCP increased cessation (6 studies) and reduced SHS exposure (4 studies). States with a CTCP decreased tobacco-related diseases and deaths (6 studies), specifically in reduced lung cancer incidence (1 study), and reduced lung cancer (3 studies) and smoking-attributable cancer (1 study) mortality. Results indicated that increased program funding was associated with greater impact on the examined tobacco-related outcomes (16 studies). Stratified analysis showed CTCPs were effective across population groups with diverse racial and ethnic backgrounds (5 studies) and varied education or socioeconomic status (6 studies).
Conclusion:
Based on CG criteria, there is strong evidence that CTCPs are effective for reducing tobacco use prevalence among adults and young people, reducing tobacco product consumption, increasing quitting, reducing SHS exposure, and reducing tobacco-related diseases and deaths, especially lung cancer. These findings are broadly applicable to the U.S. settings and population groups at the state, city, and local levels.
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MINI11.07 - The Relationship between Smoking Status and Prognostic Factors after Surgery in Lung Cancer Patients with Chronic Obstructive Pulmonary Disease (ID 1388)
17:10 - 17:15 | Author(s): M. Yotsukura, T. Ohtsuka, Y. Sugiura, Y. Hayashi, I. Kamiyama, H. Asamura
- Abstract
Background:
Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), which frequently coexists with lung cancer. For non-small cell lung cancer (NSCLC) patients with COPD, the poor prognostic factors after curative surgery and their association with smoking status are unclear.
Methods:
We enrolled 858 patients who underwent curative surgical resection for pathological stage I or II NSCLC in our institute between January 2002 and December 2012. Of these patients, those with COPD, as determined by a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7, were evaluated (n = 302). Clinical and pathological characteristics of the patients were retrospectively analyzed using the Cox regression hazards model to determine those that serve as poor prognostic factors after surgery.
Results:
The mean follow-up time was 49.3 months (±30.8 months; range, 1 to 135 months). The five-year disease-free survival rate was 70.2%, and the overall survival rate was 81.5%. Of 302 COPD patients, 243 (80.5%) had a smoking habit, whereas 59 (19.5%) did not. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion, 143 patients (47.5%) were diagnosed with stage I COPD and 159 patients (52.6%) were diagnosed with stage II COPD. The presence of a smoking habit (p = 0.010, hazard ratio [HR] 3.340, 95% confidence interval [CI] 1.334-8.359), lymphatic permeation (p = 0.001, HR 2.352, 95% CI 1.450-3.814), pathological T2 or T3 disease (p = 0.005, HR 1.666, 95% CI 1.165-2.381), and a preoperative serum carcinoembryonic antigen (CEA) value > 0.5 ng/ml (p = 0.041, HR 1.637, 95% CI 1.021-2.625) were determined to be indicators of poor recurrence-free survival in multivariate analysis. For overall survival rates, a smoking habit (p = 0.048, HR 7.527, 95% CI 1.017-55.738), a preoperative serum CEA value > 0.5 ng/ml (p = 0.001, HR 2.782, 95% CI 1.495-5.175), a histology of squamous cell carcinoma (p = 0.014, HR 2.220, 95% CI 1.175-4.193), and pathological N1 disease (p = 0.031, HR 2.505, 95% CI 1.089-5.762) were determined to be poor prognostic indicators in multivariate analysis. The disease stage as determined by the GOLD criterion was associated with neither recurrence-free nor overall survival rates. With regard to smokers, the number of pack-years did not significantly influence prognosis.
Conclusion:
We identified poor prognostic indicators for resected NSCLC in COPD patients. It should be noted that COPD patients who did not smoke had a better prognosis after surgery than those who did. Neither the number of pack-years in smokers nor the stage of COPD was related to prognosis after surgery.
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MINI11.08 - Smoking Cessation Results in a Clinical Lung Cancer Screening Program (ID 65)
17:15 - 17:20 | Author(s): A.K. Borondy Kitts, A. McKee, S. Regis, B. McKee, S. Flacke
- Abstract
- Presentation
Background:
Published results, to date, on smoking cessation and lung cancer screening have been from lung cancer screening clinical trials and/or lung cancer screening studies. Most were done before publication of National Lung Screening Trail (NLST) results. To our knowledge, this is the first report on smoking cessation and smoking relapse rates in a clinical lung cancer screening program to assess the influence of initial screening results on smoking behavior.
Methods:
Self-reported smoking status for all individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between February 1, 2014 and July 31, 2014 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at time of program entry. Point smoking cessation and relapse rates were calculated across the entire population and compared with exam results.
Results:
682 participants all of which met NCCN high-risk criteria for lung cancer were included in the study. 45% (309/682) were active smokers at program entry. The smoking cessation rate was 18.4%. Overall relapse rate was 9.9% with a relapse rate for former smokers quit for less than or equal to one year (24 of 64) of 37.5%, 14.8% for those quit for more than one year and up to two years (4 of 27), and 3.2% for those quit for more than two years (9 of 282). Initial screening exam results were not predictive of smoking status at the most recent scan (OR = 0.779, 95% CI = 0.415-1.460, p=0.435). In the group of smokers at the initial scan, screening results did not result in increased rates of smoking cessation (OR = 0.704, 95% CI = 0.308 – 1.610, p=0.405). In the group of former smokers at the initial scan, negative initial exam results did not result in increased smoking relapse rates (OR = 1.021, 95% CI = 0.364-2.860, p=0.969).
Conclusion:
Smoking cessation and relapse rates in a clinical CT lung screening program significantly exceed rates observed in the general population and do not correlate with exam results.
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MINI11.09 - Trends in Lung Cancer Mortality Attributable to Smoking, Years of Potential Life Lost and Financial Cost, Puerto Rico 1983-2010 (ID 1719)
17:20 - 17:25 | Author(s): J.C. Orengo, V. Green, H. Monsanto, C. Marques-Goyco, F. Arbelaez
- Abstract
- Presentation
Background:
During 1983, 2000 and 2004 the lung cancer deaths attributable to smoking (LCDAS) were 64.1% (>15 years old), 76% (> 35 years old) and 71% (34-65 years old), respectively. Objectives: a) LCDAS; b) Years of Potential Life Lost (YPLL) due LCDAS; c) cost associated with YPLL for the LCDAS.
Methods:
Mortality data of lung cancer (ICD-10, C33-C34) from the National Center for Health Statistics for Puerto Rico (2010) was analyzed. The prevalence of current, former and never smoking by gender was obtained from the Behavioral Risk Factor Surveillance System (2010) (CDC, US) and the Relative Risk of death dues to smoking by gender from the Cancer Prevention Study-II. The Smoke Attributable Fraction (SAF) was calculated as [p~0 ~+ p~cs ~* RR~cs ~+ p~fs ~* RR~fs ~] – 1 / [p~0 ~+ p~cs ~* RR~cs ~+ p~fs ~* RR~fs ~], where p~0 ~= prevalence of never smoker, p~cs ~= prevalence current smoker, p~fs~ = prevalence of former smoker, RR~cs, ~= Relative Risk of current smoker and RR~fs~ = Relative Risk of former smoker. The LCDAS (D~as~) were calculated as D~o~*SAF, where D~o~ = deaths observed of lung cancer 2010. To compare the data of 1983, 2000 and 2010, SAF was calculated by sex for the total population (not by age groups), with correspondent same death-risk LCDAS. YPLL used life expectancy (women=82.56 years old; men=74.85 years old). The method of willingness to pay, using three times the GDP per capita in 2010 (US$82,353), a discount rate of 3% and an annual increase of 1%, to calculate the economic cost.
Results:
In 2010, 50.3% deaths by lung cancer in women were LCDAS, men 83.7% , in 1983 women and men were 65.9% and 91.2% respectively and in 2000, 58.9% and 84.4% women and men respectively; percentage of all LCDAS (2010) was 73.3% (by sex and group of five). Total population, 2010, not by age groups 75.8%, 2000, 76.3% and1983, 82.5%. In 2010, SAF higher in women was in the age group=45-49 (smoker=13%, SAF=0.66); men was in the age group of 50-54 years (SAF=0.86) (smoker= 17.5%). In women, 1% point decreased (1983-2010) in the prevalence of smoking representing 1.5% point of decreasing LCDAS; men 1% point representing 0.3% point. Lung cancer YPLL in >35 years old represented in 2010 a total of 4,597 years [3,239 years (70.5%) were LCDAS], men accounted 2,383 years [2,014 (84.5%) years LCDAS] and women accounted 2,214 years [1,225 (55.4%) years LCDAS]. In 2010 the cost (willingness to pay) associated for men was $166 million [$139 million (84%) LCDAS], and for women was S146 million [$82 million (56%) LCDAS]. The Average Years Life Lost LCDAS for men was 10.6 years and for women 14.2 years.
Conclusion:
LCDAS have been decreasing in Puerto Rico, as demonstrated in the reduction of SAF. LCDAS occur at an earlier age in women than in men. Notwithstanding , the financial cost of LCDAS is greater in men than in women. Total financial cost for LCDAS represented 0.3% of the Puerto Rico GDP in 2010.
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MINI11.10 - Quality of Lung Cancer Treatment in Two Neighbouring Regions of Germany and Denmark (ID 374)
17:25 - 17:30 | Author(s): H.H. Storm, G. Engholm, R. Pritzkuleit, A.M.T. Kejs, A. Katalinic, J. Dunst, N.H. Holländer
- Abstract
- Presentation
Background:
A comparison of lung cancer incidence, mortality, prevalence and survival in two neighbouring regions of Germany, Schleswig-Holstein, and Denmark, Region Zealand, separated by the Fehmarn Belt, was planned based on data recorded as part of routine monitoring with a view to joint research and sharing of patients and treatment facilities
Methods:
Altogether 14,080 lung cancer patients were recorded in 2004-2010 in Schleswig-Holstein and 5,009 in Region Zealand. Excluding cases of age 90+ years or only known from death certificates, 1- and 4-year relative survival by stage and sex for the periods 2004-2006 and 2007-2009 (1-year survival only) were calculated.
Results:
A very high proportion (19%) of cases in Schleswig-Holstein was only known from death certificates contrary to Region Zealand (0%). The incidence of both, age-standardised and age-specific lung cancer, was much higher in Region Zealand versus Schleswig-Holstein (men 73/100,000 versus 68/100,000, women 58/100,000 versus 32/100,000), also reflected in the mortality figures. Lung cancer incidence was increasing among women during the observation period, more so in Schleswig-Holstein (3% estimated annual change) compared to Zealand (1%). Overall relative survival was lower in Zealand than in Schleswig-Holstein for 1-year survival in 2007-2009 (DK: 33% in men and 39% in women, versus G: 43% in men and 49% in women) and 4-year relative survival for 2004-2006 (DK: 9-13% versus G: 16-21%). Stage, sex and period specific relative survival was rather similar between countries. When restricting the analysis to patients with recorded treatment, stage-specific relative survival differences in 2007-2009 nearly disappeared.
Conclusion:
Improved data quality and comparability are needed, especially by lowering the proportion of cases only reported via death certificates in Germany. This would diminish the survival differences as a high proportion of such cases leads to an over-estimation of survival. Smoking is a strong risk factor for lung cancer and smoking prevalence 10 years before our study was high, specifically 37% in men and 22% in women in Germany and 45% in men and 38% in women in Denmark respectively. Smoking prevalence dropped to 24% in men and 21% in women in Denmark 2010, but only to 31% in men and 24% in women respectively in Germany. Such dramatic changes over a short period of time in Denmark are over time expected to be reflected in the overall incidence, mortality and even survival. International benchmarking studies are needed to understand lung cancer trends and to improve prevention and treatment of this serious cancer disease. Research presented here was partly funded by EU INTERREG 4a Fehmarn Belt 2011-2014.
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MINI11.11 - Lung Cancer and Smoking in Nepal (ID 2395)
17:30 - 17:35 | Author(s): S.C. Acharya, M.K. Piya
- Abstract
- Presentation
Background:
Smoking and Tobacco kills 15,000 people in Nepal every year. The combined prevalence of smoking and tobacco use is 56.5% in men and 19.5% in women, of whom 32.5% of men and 15.2% of women smoked cigarettes. The estimated incidence of lung cancer is 8000 per year, making it the first commonest cancer in both sexes. Lung cancer accounts for 15.4% of total cancer as per the hospital based cancer registry for both genders in Nepal.
Methods:
This prospective observational study was conducted at National Hospital and Cancer Research Centre, Nepal. Following informed consent, patients with lung cancer attending the hospital for appointments completed pre-set questionnaires about smoking only, and their stage of cancer and histological type were obtained from case notes.
Results:
A total of 116 patients completed the questionnaire between March 2012 and February 2015. 59% of the respondents were male and 41% were female. The mean age was 64 years with ranging from 31 to 81 years. The proportion of patients presenting in the different stages of lung cancer were IB (3%), IIA (2%), IIB (4%), IIIA (30%), IIIB (41%), and IV (23%). The histological type of cancer showed that 53% were Squamous Cell Carcinoma, followed by Adenocarcinoma 28%, Small cell lung Cancer 13% and Neuroendocrine tumors 4%. 85% were smokers. Of the smokers, 14% started smoking before the age of 10, 53% when they were between 11-20 years of age, 13% when they were 21-30 years and only 5% started when they were 40 years or older. Only 4% smoked more than 30 cigarettes per day, 13% smoked 21-30 per day, 32% smoked 10-20 per day and 36% patient smoked less than 10 per day. 68% used local cigarettes, 7% foreign and 10% used both. Further analysis showed that 27% used cigarettes without filters, 50% filtered and 8% used both. 28% were relighting the butt ends, 5% did this occasionally and 52% did not practice this. 13% of patients were still smoking after their diagnosis, 24% quit less than a month later, 11% quit less than a year later, 19% had already quit smoking 5 years before the diagnosis of cancer, 12% had quit 10 years before and 8% had quit 20 years before. Out of 28% of relighting, 48% patient developed cancer in compare to 52% who never relight the butt end.
Conclusion:
The results shows that majority of patients are presenting at stage III and IV. NSCLC is still on the rise in Nepal. This late presentation suggests a lack of education in the community as well as a delayed diagnosis and referral to the specialist. Focus should be given to make the population in Nepal aware about smoking and tobacco use and its link to cancer, as well as the high prevalence of lung cancer in both genders in Nepal. Focus should also be given to educating the population and non-specialist health care professionals about the symptoms of lung cancer and the importance of early presentation to improve prognosis.
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MINI11.12 - Is There Any Role for Residential Radon in Patients with Non Small Cell Lung Cancer (NSCLC) Harbouring Molecular Alterations? Preliminary Results (ID 993)
17:35 - 17:40 | Author(s): L. Mezquita, M.E. Olmedo, A. Ruano-Ravina, J.M. Fraile, A. Benito, A. Santon, S. Mayoralas, L. Gorospe, A. Cortes, S.P. Cortez, J. Munoz, A. Gomez, E. Roberts, A. Carrato, P. Garrido
- Abstract
- Presentation
Background:
World Health Organization (WHO) recommends radon concentration lower than 100 Bq/m3. Previous studies have demonstrated the correlation between high level of residential radon exposure and lung cancer especially in non-smokers patients (p.). Similarly, most of the advances in personalized therapy in NSCLC p. also occurred in non-smoker. We hypothesized that residential radon could be associated to some specific molecular alterations in NSCLC p.
Methods:
A detector alpha-track was delivered to each p. to measure radon concentration in residence for 3 months and a questionnarie to fill out. The elegible population were NSCLC p. harbouring molecular alterations (EGFR, KRAS or BRAF mutations (m)), ALK or ROS1 rearrangements (r)) and non-smoker p. treated in the Medical Oncology Department, at Hospital Universitario Ramon y Cajal, Madrid. Incident cases and prevalent cases collected from lung cancer patients database have been included from September 2014 to March 2015. We collected demographic information, smoking history, environmental exposure and clinicopathological characteristics including histology, molecular profile, stage, treatment and survival. The radon concentration was analysed using optical microscopy with radosys system 2000. EGFR, KRAS, BRAF mutation (m) were analysed using quantitative real-time polymerase chain reaction (PCR) and ALK and ROS1 rearrangements by fluorescence in situ hybridization (FISH). Statistical analysis was performed using IBM SPSS.
Results:
So far now, 48 NSCLC adenocarcinoma p. have been enrolled although only 31 have already completed radon measurement. Median age 59 years (range 33- 82); 58,1% female; 77% ECOG 0; 74,4% stage IV; 90,3% living in Madrid. Smoking habits: non-smokers 58% (9p. EGFRm, 7p. ALKr, 2p. BRAFm), light smokers 6,45% (1p. EGFRm, 1p. ALKr) and heavy smokers 35,4% (6p. EGFRm, 5p. KRASm). Median pack-years: light smokers 2,5 (2-3), heavy smokers 44 (20-80). Non-smoker p. reported 27,8% passive-smoking exposure and 44,4% childhood exposure. Radon measurement characteristics: type of building 83.9% flat; building material: 87.1% bricks. Median time of permanence in the same house: 25 years (2-55). Median height of house 3 floors (0-6). Most of measurement at bedroom (93,5%). Median of radon concentration: 103 Bq/m3 (42- 852); 51.6% over WHO recommendation. By molecular alteration: EGFRm median 91 Bq/m3 (42-164), ALKr median 128 Bq/m3 (64-852), BRAFm median 125 Bq/m3, KRASm median 80 Bq/m3 (44-149). ALKr demonstrated association with levels higher than WHO recommendation (p=0.045 Fisher's exact test).
Conclusion:
Our preliminary results show that radon concentrations in NSCLC harbouring molecular alterations are higher than WHO recommendation, particularly in patients with ALK rearrangement. Final results will help to confirm this possible association.
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MS 25 - Lung Carcinogenesis (ID 43)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:W.A. Franklin, H. Kato
- Coordinates: 9/09/2015, 14:15 - 15:45, Mile High Ballroom 2a-3b
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MS25.01 - Early Airway Disease (ID 1958)
14:20 - 14:35 | Author(s): S.M. Janes
- Abstract
- Presentation
Abstract:
In my talk I will report a prospective surveillance program, longitudinally following patients with pre-invasive disease over a 10 year period. It is the largest study of its kind and demonstrates unexpectedly high rates of both local progression to invasive cancer of high grade lesions and the development of synchronous tumours elsewhere in the lung. Further I will show data identifying both gene expression and epigenetic signatures predicting progression of these lesions. These signatures may provide the biomarker strategy we require to identify those patients with lesions at high risk of progression and therefore requiring treatment. Lung cancer accounts for more deaths than breast, prostate and colon cancers combined. Over three quarters of lung cancer patients are diagnosed at a late stage when curative treatment is not possible. Initiatives are underway to detect lung cancer earlier. CT screening of high risk smokers or ex smokers is proven to save lives through increased detection of largely early stage adenocarcinomas (1, 2). Meanwhile sputum cytometry and autofluorescence bronchoscopy of high risk individuals are under investigation as screening tools for the early detection of major airway squamous cell carcinomas in several studies. Squamous carcinogenesis is initiated by pre-invasive dysplastic lesions in the central airways and therefore lends itself to bronchoscopic evaluation. Bronchial dysplasia represents the earliest stages of what is traditionally thought to be a stepwise progression towards invasive disease commencing with squamous hyperplasia and metaplasia followed by mild, moderate, severe dysplasia (SD) and carcinoma-in-situ (CIS) with lesions possessing a greater mutational burden at each stage (WHO classification) (Figure 1). With progression of the lesion there are characteristic morphological changes and increasing cytological disarray. Initial changes affect only the basal epithelium, whilst ‘full thickness’ change is seen in the more advanced CIS. Once the basement membrane has been breached, invasive squamous cell carcinoma has developed. Figure 1 Our early findings, and those of others, have challenged this traditional stepwise model. With longitudinal follow up, few low grade dysplasia lesions (LGD: hyperplasia, metaplasia mild and moderate dysplasia) are seen to progress and largely remain indolent or often regress. High grade dysplasia lesions (HGD: SD and CIS) however, more frequently persist or progress to invasive disease. Bronchial dysplastic lesional destiny is unpredictable and despite research examining the genetic and epigenetic changes that occur, as yet no robust biomarker is able to determine which lesions will continue to progress to invasive disease. Low grade lesions rapidly progressing to cancer have been reported, and these rare lesions have been found to possess a high degree of chromosomal instability including DNA copy number alterations even at a metaplastic stage, seeming to confer a committed course to cancer development. It is likely that close analysis of these rare lesions and other high grade lesions that progress will lead to greater biological insight regarding key lung cancer driver mechanisms. Autofluorescence bronchoscopy (AFB) using blue-violet excitation light has made progress in facilitating not only the detection and delineation of extent of early stage invasive cancers in the airway but also the identification of precancerous central airway lesions that are generally missed on CT. AFB detection of precancerous lesions has been shown to have sensitivity exceeding that of white light bronchoscopy (WLB) alone. The sensitivity of combining AFB with WLB improves detection of bronchial premalignant and malignant lesions up to 96.8% versus 76.3% for WLB alone, whilst corresponding negative predictive values are 97.2% versus 83.1% (3). Treatment of precancerous lesions might be expected to lead to improved survival in those patients harboring them. However our lack of knowledge of the natural history of these lesions, the appearance of new lesions, the regular occurrence of separate lung primaries and the lack of interventional studies in this area leaves the role of early intervention (both surgical and local tissue sparing procedures) under dispute. Due to this poverty of knowledge, our strategy, in keeping with previously published studies, has been the surveillance of all grades of dysplasia. These include our own, initial observations that suggest a low rate of lesion progression but high synchronous invasive cancer occurrence (4, 5). This early experience indicates patients with preinvasive disease are at a globally high risk of developing lung cancer, although not necessarily from the lesion under observation and multiple lesions both centrally and peripherally commonly develop over time. Due to the shared risk factor of tobacco smoke exposure, patients often have significant respiratory and cardiovascular co-morbidity and radical treatment of preinvasive disease may lead to insufficient lung capacity to offer curative intervention to future invasive lung cancer. 1. NCCN Clinical Practise Guidelines in Oncology. Lung Cancer Screening. Version http://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdf 2. National Lung Screening Trial Research Team, Aberle DR, Berg CD, Black WC, Church TR, Fagerstrom RM, Galen B, Gareen IF, Gatsonis C, Goldin J, Gohagan JK, Hillman B, Jaffe C, Kramer BS, Lynch D, Marcus PM, Schnall M, Sullivan DC, Sullivan D, Zylak CJ. The National Lung Screening Trial: overview and study design.Radiology. 2011 Jan;258(1):243-53. 3. Hanibuchi M, Yano S, Nishioka Y, Miyoshi T, Kondo K, Uehara H, Sone S. Autofluorescence bronchoscopy, a novel modality for the early detection of bronchial premalignant and malignant lesions. J Med Invest. 2007 Aug;54(3-4):261-6. 4. George JP, Banerjee AK, Read CA, O'Sullivan C, Falzon M, Pezzella F, Nicholson AG, Shaw P, Laurent G, Rabbitts PH. Surveillance for the detection of early lung cancer in patients with bronchial dysplasia. Thorax. 2007 Jan;62(1):43-50. 5 Auerbach O, Stout AP, Hammond EC, et al. Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med 1961;265:255–67.
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ORAL 07 - Lung Cancer Pathogenesis (ID 91)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:J. Sage, E. Brambilla
- Coordinates: 9/07/2015, 10:45 - 12:15, 102+104+106
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ORAL07.03 - MMP12 and LMO7 Are Key Genes Involved in the Early Pathogenesis of Squamous Cell Carcinoma of the Lung (ID 1173)
11:07 - 11:18 | Author(s): S.M. Janes
- Abstract
Background:
Lung cancer is the most lethal cancer type worldwide. In order to increase patient survival it is important to improve our understanding of the early changes associated with lung cancer progression. The progression of lung squamous cell carcinoma (SqCC) from pre-invasive lesions involves a series of histological changes which includes squamous metaplasia, mild, moderate and severe dysplasia, and carcinoma in situ (CIS). In these pre-invasive lesions the basement membrane is intact and there is no possibility of metastatic spread, which is in contrast to SqCC where there is the potential for metastasis as soon as invasion occurs. Our laboratory has a unique cohort of patients with pre-invasive lung SqCC lesions. Within this cohort there is a discrepancy between the prevalence of pre-invasive lesions and the incidence of invasive lung cancer, which suggests that not all pre-invasive lesions progress to invasive carcinomas. This tissue collection forms an internationally unique resource of lesions and will shed light on the molecular characteristics of lesions that progress compared to those that either regress or remain stable. The aim of this study was to identify and characterize key genes involved in the early pathogenesis of lung SqCC.
Methods:
Following histological review by two histopathologists to confirm that pre-malignant tissue is present in the biopsy specimens, the epithelial component of interest was laser-capture micro-dissected. This is vital in order to eliminate any cross-contamination from unwanted cells and to ensure that pre-invasive CIS specific gene expression profiles are generated. We have performed genome-wide gene expression Illumina’s Whole-Genome DASL® arrays in 20 progressive and 19 regressive pre-invasive lung SqCC lesions. The protein expression of Matrix metallopeptidase 12 (MMP12) and LIM domain 7 (LMO7) was also determined in the 39 pre-invasive lung cancer lesions by immunostaining analysis. The functional role of MMP12 and LMO7 in cell migration and invasion was demonstrated by MMP12 and LMO7-shRNA knockdown in different squamous cell carcinoma cell lines and human bronchial epithelial cells (HBECs), respectively.
Results:
We found 939 genes significantly differently expressed between the progressive and the regressive pre-invasive lung SqCC lesions. We identified a remarkably elevated expression of a spectrum of genes in the progressive lung SqCC lesions involved in different related cancer pathways including chromosome instability, p53 signalling and Wnt/β-catenin signalling. MMP12 and LMO7 were found within the highest significantly differently expressed genes and were therefore chosen to pursue studies focused on understanding the potential mechanisms leading to the development of lung SqCC. In agreement with the gene expression data the expression of MMP12 and LMO7 proteins were up-regulated and down-regulated, respectively, in progressive when compared with regressive lesions. Inhibiting MMP12 by MMP12 knockdown significantly reduced the migration and invasion of different squamous cell carcinoma cell lines (A431, H357 and H376). We also established HBECs knockdown targeting LMO7. We observed a significant increase in the migration and invasion of HBECs cells in the LMO7 shRNA knockdown compared to control.
Conclusion:
Our results suggest that MMP12 and LMO7 may be potential therapeutic markers for lung cancer at early stage.
