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G. Kovács
Moderator of
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OA 06 - Global Tobacco Control and Epidemiology I (ID 662)
- Event: WCLC 2017
- Type: Oral
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 9
- Moderators:G. Kovács, Yun Fan
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 511 + 512
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OA 06.01 - Costs and Cost-Effectiveness of Smoking Cessation Within an Organized CT Lung Cancer (LC) Screening Program (ID 9642)
15:45 - 15:55 | Presenting Author(s): William Kenneth Evans | Author(s): C. Gauvreau, W. Flanagan, S. Memon, N. Fitzgerald, John R Goffin, A. Miller
- Abstract
- Presentation
Background:
Low-dose CT (LDCT) screening of smokers at high risk of developing lung cancer has been shown to reduce LC-specific and overall mortality. A retrospective analysis of the National Lung Screening Trial (NLST) data suggests that smoking cessation contributed to the mortality reduction. Pilot LDCT screening programs are being implemented in Ontario with smoking cessation integrated. The Canadian Partnership Against Cancer with Statistics Canada have developed a microsimulation model (OncoSim-LC, version 2.5) that projects the impact of cancer control measures on LC incidence, mortality and cost. Assuming that each annual visit for LDCT is a teachable moment to promote smoking cessation, we have modelled the potential cost and cost-effectiveness of integrating cessation into an organized screening program.
Method:
OncoSim-LC incorporates Canadian demographic characteristics, risk factors, cancer management approaches and outcomes and resource utilization to assess clinical, economic and healthcare system impacts. We compare a base case of organized screening with no cessation to various scenarios of screening with cessation. Modelling assumptions included: annual screening of 55-74 year olds with 30+ pack year smoking history, target participation rate reached over 10 years; one cessation intervention (nicotine replacement therapy + varenicline + 12 weeks of counselling) costs $490; up to 10 cessation attempts per eligible individual dependent on screening encounters; a permanent quit rate of 5% per cessation attempt. Cost-effectiveness was estimated with a lifetime horizon, health system perspective and 1.5% discount rate. Costs are in 2016 CAD.
Result:
Cessation within a screening program with 60% recruitment and 70% rescreening (adherence) would cost approximately $76 million (undiscounted) per year for 2017-2036 or 8% of the total cost of screening, treatment and cessation. Compared to screening with no cessation, approximately 110 fewer incident cases and 50 fewer lung cancer deaths would occur on average per year for 2017-2036 and cost $14,000/QALY (lifetime horizon). 90% recruitment and 80% rescreening would result in 260 fewer deaths and cost of $24,000/QALY. At a doubled permanent quit rate of 10%, screening with cessation would cost $6,000/QALY. A 50% increase in the cost of the cessation intervention would decrease cost-effectiveness to $22,000/QALY.
Conclusion:
Based on the OncoSim-LC model, a cessation program within an organized LDCT screening program would cost well under $50,000/QALY even over multiple quit attempts. Integrating robust smoking cession initiatives within a LDCT screening program could save lives and be relatively cost-effective.
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OA 06.02 - Final Report of the INHERIT EGFR Study - 33 Unrelated Kindreds Carrying Germline EGFR Mutations (ID 9370)
15:55 - 16:05 | Presenting Author(s): Geoffrey R. Oxnard | Author(s): J.C. Heng, R. Chen, D.R. Koeller, K. Shane-Carson, R.H. Morgan, G.L. Wiesner, J.E. Garber
- Abstract
- Presentation
Background:
Anecdotal reports of families carrying germline EGFR mutations force us to reconsider our understanding of inherited lung cancer risk in non-smokers. We launched this prospective trial (NCT01754025; ALCMI-002) to remotely enroll and characterize these rare families.
Method:
Eligible subjects were recruited at participating cancer centers or through an online referral system. Following consent (in person or by phone), subjects received genetic counseling and sequencing of saliva or blood for germline EGFR mutations. Cancer specimens and CT scans were additionally analyzed when available.
Result:
Between 12/2012-6/2017, 105 participants were enrolled from 30 US states. Germline EGFR mutations were found in 63% of patients (31 of 49) with EGFR T790M in their lung cancer at diagnosis, and in 62% (16 of 27) and 44% (4 of 9) of first- and second-degree relatives of germline carriers. Pedigrees were available for 32 unrelated kindreds (31 germline T790M, 1 germline R776H): 4 with no family history of lung cancer, 8 with a family history of lung cancer in non-smokers, 18 with multiple relatives with lung cancer. Characteristics of 31 lung cancer probands: median age of lung cancer diagnosis was 57 (range 28-82); 81% white, 19% black; 52% never-smokers; 65% stage IV at diagnosis; 65% were from states in or bordering the US Southeast. Tumor genotyping revealed somatic EGFR co-mutations in 29 (94%) of probands: 6 exon 19 del, 12 L858R, 6 G719X, 1 exon 19 del & G719R, 1 L861Q, 2 H773R, 1 V774M. Imaging analysis suggests a unique pattern of cancer evolution including an indolent multi-focal nodular phase which then progresses to lymph nodes and then remote metastatic disease. Of 8 probands with sensitizing EGFR co-mutations treated with osimertinib, no unexpected toxicities were seen, and 4 have had durable benefit exceeding 12 months. Of 9 relatives with germline EGFR mutations and CT imaging available, 2 have a lung cancer diagnosis and 6 others have lung nodules.
Conclusion:
This study confirms the high likelihood of a germline mutation in lung cancer patients with EGFR T790M detected at diagnosis, and suggests a risk of lung nodules and lung cancer in germline carriers. The regional enrichment in the US Southeast suggests a possible founder effect; haplotyping is planned. A registry is under development to continue follow-up of these rare individuals. Further investigation of germline risk alleles associated with lung cancer risk in non-smokers is needed. Funding: Bonnie J. Addario Lung Cancer Foundation, Conquer Cancer Foundation of ASCO.
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OA 06.03 - Comorbidity and Competing Causes of Death attenuate outcomes in the NLST. (ID 8606)
16:05 - 16:15 | Presenting Author(s): Robert P Young | Author(s): Raewyn J Hopkins, G.D. Gamble
- Abstract
- Presentation
Background:
In the National Lung Screening Trial (NLST), annual CT screening reduced lung cancer-specific mortality by 20% and all-cause mortality by 7% relative to chest x-ray (CXR) screening. However, in contrast to other screening approaches, recommendations for CT screening for lung cancer is limited to older heavy smokers, where the risk of death from all smoking-related complications is high, relative to the unscreened population. In the NLST, airflow limitation affects 35% of screening participants and is associated with a 2-4 fold increase risk of lung cancer. We have recently shown that for screening participants with COPD, the reduction in lung cancer-specific mortality with CT screening is only half that seen in those with no COPD (15% vs 28%). We hypothesise that this reduction is due in part to a “competing cause of death” effect.
Method:
Using 10,054 subjects from the ACRIN-NLST sub-study, the current study aimed to compare disease-specific mortality according to the severity of airflow limitation at baseline to better understand it’s relationship with dying of lung cancer and dying of other smoking-related diseases. We also examined this relationship according to baseline risk of lung cancer, using the Brock (Lung cancer risk) Model, and outcomes from screening.
Result:
After 6.4 years of follow-up, there were 699 deaths; 189 (27%) attributed to lung cancer, 166 (24%) to cardiovascular disease, 61 (9%) to respiratory disease and 150 (21%) to other cancers. After stratifying the 10,054 subjects according to severity of airflow limitation (baseline FEV1%predicted and GOLD grade), we found that the risk of dying of lung cancer and risk of dying of other diseases diverged favouring a stronger relationship with non-lung cancer causes. After stratifying the 10,054 subjects according to their risk of lung cancer (tertiles), we found that CT screening in those at highest risk (highest tertile) had only a 12% reduction in lung cancer-specific deaths compared to 23-24% in other lower risk tertiles. This was associated with higher deaths from cardiovascular disease, respiratory disease and other cancers.
Conclusion:
In a CT screening study, where smokers were followed for a mean of 6.4 years, we found worsening lung function and higher underlying risk for lung cancer was associated with a greater tendency to die of causes other than lung cancer. We suggest smokers at the greatest risk for lung cancer, and those with worse lung function, benefit less from CT screening due to a “competing cause of death” effect.
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OA 06.04 - Discussant - OA 06.01, OA 06.02, OA 06.03 (ID 10787)
16:15 - 16:30 | Presenting Author(s): Anthonie Van Der Wekken
- Abstract
- Presentation
Abstract not provided
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OA 06.05 - Socioeconomic Factors Affecting Outcomes in Non-Small Cell Lung Cancer (NSCLC): A Large Population-Based Analysis (ID 9049)
16:30 - 16:40 | Presenting Author(s): Yanyan Lou | Author(s): Bhagirathbhai Dholaria, A.E. Soyano, D. Hodge, S. Ailawadhi
- Abstract
- Presentation
Background:
Disparities exist in cancer outcomes. NSCLC outcomes have improved in recent years but effects of socioeconomic factors have not been reported.
Method:
The National Cancer Database with NSCLC incident cases between 2004-2013 was analyzed. Overall survival (OS) was explored by several available factors with a focus on race and socioeconomic factors.
Result:
A total of 1,150,722 NSCLC patients were included with majority White (86.4%) followed by Black (10.6%) and a smaller proportion of Asians and Hispanics. Patients were evenly distributed among income quartiles and majority were insured (96.7%), lived in a metro area (81.7%) and treated at non-academic facilities (68.5%). Overall median OS was 13.1 months and significantly better for Asians (18.2 months) and Hispanics (16.6 months) as compared to Whites (13.2 months) and Blacks (11.5 months). (Figure 1, p<0.001) Outcomes were worse with higher comorbidity score, TNM stage and treatment at community or high-volume facility. Socioeconomic factors other than race associated with worse outcome included lower education and median income, uninsured status and Central geographic region. (Table 1) Figure 1 Figure 2
Conclusion:
In this largest analysis thus far, patient race and socioeconomic factors were found to significantly influence NSCLC survival. These must be addressed for equitable healthcare benefit and outcomes.
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OA 06.06 - Chr15q25 Locus Confers Risk of Lung Cancer, COPD and Smoking: Triple Whammy Effect in the ACRIN NLST Sub-Study (N=9,270) (ID 8611)
16:40 - 16:50 | Presenting Author(s): Raewyn J Hopkins | Author(s): F. Duan, E. Greco, C. Chiles, G.D. Gamble, D.R. Aberle, Robert P Young
- Abstract
- Presentation
Background:
Several large genetic studies have consistently linked the cholinergic nicotinic receptor polymorphism (CHRNA3/5, rs 16969968) to lung cancer and smoking addiction. However, we have shown that this genetic variant was also independently associated with susceptibility to chronic obstructive pulmonary disease (COPD). To date this observation, independently linking CHRNA3/5 polymorphism to both COPD and lung cancer, has not been tested prospectively in a cohort study. Using 10,054 subjects from the ACRIN-NLST cohort, a sub-study of the NLST that recruited high risk smokers and followed them for an average of 6.4 years, we examined the association between the CHRNA3/5 variant in the development of lung cancer relative to its role in COPD and lifelong smoking exposure.
Method:
We compared the frequency of the high risk AA genotype in our cohort of 10,054 high risk smokers according to their smoking status, lung function and COPD status. We also compared the lung cancer incidence rate according to the CHRNA3/5 genotype. Lastly we used stepwise logistic regression and mediation analysis to examine the role of the AA genotype of the CHRNA3/5 variant in smoking exposure, COPD and lung cancer.
Result:
Relative to healthy smoking controls, the AA genotype was associated with the presence of COPD (OR=1.3, P<0.001) and the development of lung cancer overall (OR=1.5, P<0.01), lung cancer with pre-existing COPD (OR=1.5, P=0.04), lung cancer with no COPD (OR=1.5, P=0.04). Compared to the GG and AG genotypes, the AA genotype was associated with (a) lower FEV1%pred, lower FEV1/FVC and a 19% increase in risk of COPD; and (b) greater cigs/day, pack years exposure and a 47% increased risk of lung cancer. No differences were found for age, gender, smoking duration, years since quitting and current smoking status. In stepwise logistic regression, we found that age, BMI, AA genotype, smoking exposure and lung function were independently associated with getting lung cancer. In the mediation analyses we found that the AA genotype was independently associated with smoking (OR=1.42,P<0.05), COPD (OR=1.25,P<0.05) and getting lung cancer (OR=1.37, P<0.05).
Conclusion:
This is the first prospective study to confirm that while the CHRNA3/5 variant is associated with lung cancer, more importantly this variant is also independently associated with airflow limitation (COPD). It is also the first cohort study to show that while this genetic variant is also associated with smoking exposure (triple whammy effect), this is independent of its effects on predisposition to both COPD and lung cancer.
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OA 06.07 - Survival Trends Among Non-Small Cell Lung Cancer (NSCLC) Patients Over A Decade: Impact of Initial Therapy at Academic Centers (ID 10149)
16:50 - 17:00 | Presenting Author(s): Yanyan Lou | Author(s): Bhagirathbhai Dholaria, S. Ailawadhi, A.E. Soyano, D. Hodge, R. Manochakian, M.E. Menefee, E. Johnson, M. Thomas, S. Ko, R.C. Miller, M. Johnson, N. Patel, K. Mody, R. Joseph
- Abstract
- Presentation
Background:
Treatment of NSCLC is rapidly advancing and academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported.
Method:
The National Cancer Database (NCDB) with NSCLC incident cases between 2004-2013 was used. Overall survival (OS) was plotted by year of diagnosis and type of treatment facility, accounting for several available factors in NCDB.
Result:
A total of 1,150,722 NSCLC patients were included and separated by initial treatment facility type (academic: 31.5%, non-academic: 68.5%). Several characteristics were significantly different between the two cohorts (Table 1). Median OS for all patients was 13.1 months and improved significantly for those diagnosed in 2010-2013 (14.8 months) as compared to 2004-2009 (12.4 months) (p<0.001). Treatment at academic centers was associated with reduced risk of death [Multivariate HR=0.91 (95% CI 0.906-0.919), P<0.001]. Four-year OS for academic and non-academic cohorts was 25% and 19%, respectively (p<0.001), the difference more pronounced in stage 1-3. (Figure 1) Figure 1 Figure 2
Conclusion:
In this largest analysis thus far, NSCLC survival has improved over time and type of treatment facility significantly influences survival. Factors influencing treatment facility choice should be addressed for easier access to academic centers.
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OA 06.08 - Is Lung Cancer Screening Associated with a Negative Psychological Impact? (ID 9879)
17:00 - 17:10 | Presenting Author(s): Ben Young | Author(s): M. Clark, L. Bedford, R. Das Nair, J. Robertson, K. Vedhara, D. Kendrick
- Abstract
- Presentation
Background:
Lung cancer screening can reduce lung cancer mortality by 20%. It is currently recommended in the USA, but not in the UK and ensuring any potential psychological harm is minimised is important. Current evidence is limited to the psychological impact of CT lung cancer screening. This study assesses psychological responses in the Early Cancer Detection Test - Lung Cancer Scotland Study (ECLS Study), whose participants have a tumour antibody blood test (Early CDT®-Lung test) and CT scans only for those with positive blood tests.
Method:
ECLS study participants were randomised to an Early CDT®-Lung test group or a control group. A sample (n=1032) participated in a nested psychological outcomes study. Questionnaires measured psychological responses (positive and negative affect scale (PANAS), lung cancer worry scale (LCWS) and impact of events scale (IES)) at baseline and 1, 3, 6 and 12 months post-trial recruitment. Psychological responses over time were assessed using multilevel modelling and compared between those in the control group, the test-positive group and the test‑negative group.
Result:
In total, 350, 361 and 321 participants were in the control, test-negative and test-positive groups respectively. Follow-up questionnaire completion rates were ≥90% at all time-points. Baseline psychological measures did not differ significantly between groups. Significant differences were found between PANAS scores, but absolute differences between the groups were very small and unlikely to be clinically significant. The IES avoidance and intrusion scores were significantly higher in the positive than the negative group at all time-points and at 1, 3 and 6 months respectively. However, median scores for both subscales at all the time-points were in the subclinical range. Anxiety about future tests and treatment at 1 month was significantly higher in the test-positive group than the control (OR (95%CI) 3.55 (1.70, 7.41)), or the negative group (OR (95%CI) 5.74 (2.69, 12.2)). Worry about getting lung cancer in the future was significantly higher in the test-positive than the test-negative group at 1 month (OR (95%CI) 2.61 (1.35, 5.02)), 3 months (OR (95%CI) 2.52 (1.30, 4.87)) and 6 months ((OR (95%CI) 2.98 (1.53, 5.82)).
Conclusion:
Lung cancer screening using a blood test followed by CT scanning for test-positive individuals does not appear to impact on affect, intrusive thoughts or avoidant behaviour to a clinically important degree. However, anxiety about future tests and treatment and future worry about lung cancer needs to be addressed if lung cancer screening is implemented in the UK.
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OA 06.09 - Discussant - OA 06.05, OA 06.06, OA 06.07, OA 06.08 (ID 10788)
17:10 - 17:25 | Presenting Author(s): Norihiko Ikeda
- Abstract
- Presentation
Abstract not provided
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