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Christian Klaus Manegold
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MA 18 - Global Tobacco Control and Epidemiology II (ID 676)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 15
- Moderators:H. Kawai, Christian Klaus Manegold
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 511 + 512
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MA 18.01 - Driving Improvements in Cancer Care Ontario's Smoking Cessation Initiative for Cancer Patients in Ontario, Canada (ID 10401)
15:45 - 17:30 | Presenting Author(s): Meredith Elana Giuliani | Author(s): William Kenneth Evans, A. Peter, R. Truscott, E. Cameron, N. Schwartz, M. Haque, M. Bassier-Paltoo, S. Khan
- Abstract
- Presentation
Background:
Substantial evidence exists that quitting smoking after a cancer diagnosis can result in improved treatment efficacy and safety, decreased risk of recurrence and second primary cancers, and lower mortality. Based on this evidence, Cancer Care Ontario (CCO) implemented a smoking cessation program for new ambulatory cancer patients in Ontario’s 14 Regional Cancer Centres (RCCs) in 2014. Implementation is monitored centrally by CCO using performance indicators and monthly discussions with regional champions. Significant variation in implementation processes and performance metrics amongst RCCs highlighted a need for quality improvements.
Method:
Funding received from the Canadian Partnership Against Cancer enabled CCO to undertake a series of initiatives to enhance provider and patient education and to standardize processes. Based on program learnings and emerging evidence, the program model was revised from 5As (Ask, Advise, Assess, Assist, Arrange) to 3As (Ask, Advise, Act), and site-specific recommendations were provided to support consistency in implementation. Patient-facing materials, an on-line learning module, scripts and videos were developed to educate healthcare providers and patients on the health benefits of smoking cessation in order to improve rates of screening and referrals to cessation services. Importantly, two performance indicators have been included on CCO’s Regional Scorecard, which measures performance against targets and determines an RCC’s overall performance ranking within the province.
Result:
Performance on the Tobacco Use Screening indicator (proportion of new cancer patients screened for tobacco use) was 42.0% across Ontario in April 2015 when first included on the Scorecard. By March 2017, performance had improved to 62.7%, with significant improvements seen among the lowest-performing RCCs. The Accepted a Cessation Referral indicator (proportion of tobacco users who accepted referral to cessation services) improved only modestly from 19.7% in Q1 of 2016/17 to 23.4% in Q4. This indicator will be added to the Regional Scorecard starting in 2017/18. Both indicators are discussed at the quarterly performance reviews with the Regional Vice-Presidents responsible for cancer services. In 2016/17, lung cancer patients accounted for the largest percentage of current users of tobacco by tumour site (21.9%); in addition, almost a quarter of all patients accepting a referral (24.3%) were lung cancer patients.
Conclusion:
The CCO performance Scorecard is a strong driver of quality improvement. CCO is encouraged by regional enthusiasm to adopt the refined 3As model, and anticipates further improvements in the performance metrics, especially in the number of tobacco users who accept referral to cessation services.
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MA 18.02 - Outcomes of Integrating Smoking Cessation Counseling in a Lung Screening Program (ID 8575)
15:45 - 17:30 | Presenting Author(s): Matthew A Steliga | Author(s): B.G. Fortson, A. Nagy, P.L. Franklin, C. Barone, E.L. Boone
- Abstract
- Presentation
Background:
The National Lung Screening Trial demonstrated that lung screening reduces lung cancer mortality. In our lung screening program, the incidence of lung cancer is a small percentage (2.3% (10/440)). A more common, treatable, and potentially overlooked condition in this population is nicotine addiction (70.2% smoking (309/440) in our program). It has been widely postulated that lung cancer screening provides a “teachable moment” for smoking cessation. Smoking cessation counseling has been integrated in our lung cancer screening program since 2014. The goal is to report outcomes of integrating smoking cessation in the lung screening program.
Method:
In our lung screening program, all scheduling is done by a single coordinator who is both a Nurse Practitioner and a Certified Tobacco Treatment Specialist (CTTS). A call to schedule the scan is done and initial basic tobacco cessation intervention is integrated into every call. Further follow up as in depth face-to-face counseling is offered at the point of the scan, by the coordinator or other CTTS. Tobacco cessation follow up may be further integrated into telephone calls to give patients screening results. Patients noted to be smoking at the time of the screen (n=103) were surveyed by telephone by a researcher to determine whether they had quit smoking, reduced, or made no changes. Further chart review yielded 107 additional patients unable to be reached by the researcher, but data regarding smoking was available from medical records.
Result:
Of the patients able to be contacted by telephone, 11.7% (12/103) quit smoking, 53.4% (55/103) had reduced the amount they were smoking, and 35.0% (36/103) had made no changes. Additional chart review yielded 107 patients screened and 14.0% (15/107) had documented cessation at least one year after screening.
Conclusion:
Integration of tobacco cessation counseling into our lung screening program led to an overall quit rate of 12.9% (27/210) and of those interviewed, 60.4% (55/91) of those who did not quit, reduced the amount that they smoked. While this may sound modest, this population is heavily addicted, and unaided cessation has poor success rates, often cited as less than 4%. This supports integration of cessation counseling as a potential model for improving smoking cessation in the lung screening population. Further work with integrating pharmacotherapy and more frequent regular follow up may yield even higher success rates.
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MA 18.03 - Role of Electronic Cigarettes in Lung Cancer Prevention Among Smokers (ID 10261)
15:45 - 17:30 | Presenting Author(s): Maciej Lukasz Goniewicz
- Abstract
- Presentation
Background:
Although the best way for smokers to avoid the health risks associated with smoking is to quit smoking altogether, for those who do continue to smoke the application of a harm reduction strategy could result in substantial reductions in mortality and morbidity. One such approach for continuing smokers would be to promote the substitution of alternative, less toxic means of delivering nicotine, assuming that these were proven to be less hazardous than tobacco smoking and did not cause any additional health risks. Electronic cigarettes, commonly called "e-cigarettes", represent a new stage in which nicotine is delivered in a method that simulates smoking but without involving a tobacco combustion process.
Method:
We measured levels of selected carcinogens and toxicants in aerosol generated from e‑cigarettes. Using in vitro systems, we studied toxicological effects of e-cigarette aerosol on bronchial epithelial cells. In a longitudinal within-subjects observational study, we assessed exposure to nicotine and selected carcinogens in cigarette smokers who switched to e-cigarettes. In a cross-sectional study, we compared exposure to nicotine and carcinogens among smokers of combustible cigarettes only, e-cigarette user, former smokers with long-term nicotine replacement therapy (NRT) use, and dual users of both combustible cigarettes and e-cigarettes.
Result:
Nicotine solutions used in e-cigarettes vary with respect to concentrations of toxicants. We identified a number of toxicants in e-cigarettes; however the levels of these toxicants were orders of magnitude lower than those found in cigarette smoke. In vitro studies showed that cell viability and metabolic activity were more adversely affected by conventional cigarettes than e-cigarettes. In longitudinal observational study of smokers, we found that after switching from tobacco to e-cigarettes nicotine exposure is unchanged while exposure to toxicants is substantially reduced. Long-term e-cigarette use, but not dual use of e-cigarettes with combustible cigarettes, is associated with substantially reduced exposure levels to carcinogens relative to smoking combustible cigarettes.
Conclusion:
Although it cannot be said that currently marketed e-cigarettes are safe, e-cigarette aerosol is likely to be much less toxic than cigarette smoke. The devices likely pose less direct hazard to the individual smoker than tobacco cigarettes and might help smokers quit smoking or reduce harm by smoking fewer cigarettes. The use of e-cigarettes as a harm reduction strategy among cigarette smokers who are unable to quit, warrants further studies. Further research is needed to evaluate long term effects of switching, including the health effects of continued use of e-cigarettes.
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MA 18.04 - Changes in Smoking Behaviour in the Early Cancer Detection Test Lung Cancer Scotland (ECLS) Study (ID 8539)
15:45 - 17:30 | Presenting Author(s): Ben Young | Author(s): L. Bedford, K. Vedhara, R. Das Nair, J. Robertson, D. Kendrick
- Abstract
- Presentation
Background:
Lung cancer screening might be a ‘teachable moment’ for smoking cessation or conversely could provide a ‘license to smoke’. Such effects should be considered in the overall benefits and harms of screening. Existing evidence of the impact of screening on smoking is mixed.
Method:
A randomised controlled trial of a blood autoantibody test (EarlyCDT-Lung) for the early detection of lung cancer was conducted in 12,210 smokers and ex-smokers in Scotland, UK. The test allowed risk stratification for targeting of a chest X-ray and repeat CT scans. Sub-samples of positive test (n = 321), negative test (n = 361) and control (n = 350) participants completed questionnaires before screening, after receipt of blood test results and at 3, 6 and 12 months post-screening. They self-reported smoking point prevalence, attempts to quit, number of cigarettes smoked per day and the Heaviness of Smoking Index. Multi-level regression analyses, adjusted for confounders, explored differences in smoking over time between screened and control arms and between positive test, negative test and control groups.
Result:
Preliminary results show no statistically significant differences in smoking prevalence between the screened and control arms over time. There was a reduction in smoking prevalence of borderline statistical significance in the positive test group versus controls across all time points (OR 0.46, 95% CI 0.21-1.03). This difference reduced when assuming non-responding smokers were still smoking (OR 0.55, 95% CI 0.25-1.19). Significantly more smokers in the positive test group had recently attempted to stop smoking at 3 months compared to controls (OR 2.29, 95% CI 1.04-5.04). Positive test group smokers were significantly less likely to report smoking 20 or more cigarettes a day than controls across all time points (OR 0.32, 95% CI 0.14-0.69). Negative test group smokers were more likely to score moderate/high/very high on the Heaviness of Smoking Index compared to controls at 6 months. This difference was statistically significant before adjusting for confounders but the adjusted model was no longer significant (OR 2.51, 95% CI 0.90-6.97).
Conclusion:
There was no effect of lung cancer screening on smoking prevalence. The findings indicate a positive test result can be a teachable moment for smoking cessation. They also highlight the short term risk of heavier smoking after a negative test result. This is an important area for further research to ensure negative lung cancer screening test results do not inadvertently promote continued and heavier smoking.
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MA 18.05 - Discussant - MA 18.01, MA 18.02, MA 18.03, MA 18.04 (ID 10789)
15:45 - 17:30 | Presenting Author(s): Emily Stone
- Abstract
- Presentation
Abstract not provided
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MA 18.06 - Clinical Prognostic Model for Older Patients with Advanced Non-Small Cell Lung Cancer (ID 8113)
15:45 - 17:30 | Presenting Author(s): Apar Kishor Ganti | Author(s): X. Wang, Thomas E. Stinchcombe, Y. Wang, Karen Kelly, R. Paulus, Jeffrey Bradley, Suresh S Ramalingam, H.J. Cohen, Everett E Vokes, H. Pang
- Abstract
- Presentation
Background:
The median age at diagnosis of lung cancer is 70 years. Older patients are often not prescribed standard therapy. Due to multiple competing causes of death, older patients often do not demonstrate a benefit in overall survival (OS). It is important to know which older patients would actually be candidates for aggressive therapy based on their prognosis, and to develop a simple prognostic model that can help clinicians determine individual prognosis.
Method:
Data on patients enrolled on 38 NCI-sponsored cooperative group clinical trials of advanced non-small cell lung cancer (NSCLC) from 1991 to 2011 were analyzed. Multivariable Cox PH model was built with a stepwise procedure with all potential predictors: age, sex, race, ethnicity (Hispanic or non-Hispanic), performance status, initial stage, BMI, and weight loss in the past 3/6 months. We derived a prognostic score using the estimated Cox PH regression coefficient in the training set. To assess the performance of our prognostic model, we calculated the area under receiver operating characteristic (ROC) curve of 1- and 2-year survival in the testing set.
Result:
The final analysis included 1454 NSCLC patients ≥70 years of age. These patients were randomly divided into a training set (n=962) and a testing set (n=492). The prognostic risk score was calculated as: 3 (if male) + 3 (if PS=1) + 8 (if PS=2) + 11 (if initial stage=IV) + 4 (if weight loss). Patients were classified into three prognostic groups by tertiles: good (0-6), intermediate (7-14) and poor (≥15). The median OS in the three groups in the testing set were: 14.6 months (95% CI, 12.2-18.5); 12.2 months (95% CI, 10.7-14.4) and 7.0 months (95% CI, 5.6-8.9), respectively. Despite its simplicity, the present model had area under the 1-year and 2-year ROCs (0.63 and 0.68, respectively) that were higher than existing models.
Conclusion:
Male gender, poor performance status, distant metastases and weight loss immediately prior to diagnosis predict for poor OS in older patients with advanced NSCLC. This study proposes a simple prognostic model for older adults with advanced NSCLC based on basic clinical characteristics that are part of the routine evaluation process for every patient with NSCLC.
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MA 18.07 - Disparity in Prognostic Factors After Pulmonary Resection in Non-Small Cell Lung Cancer Between Asian and White Patients (ID 10080)
15:45 - 17:30 | Presenting Author(s): Apichat Tantraworasin | Author(s): E. Taioli, B. Liu, N. Alpert, A.J. Kaufman, R. Flores
- Abstract
- Presentation
Background:
Overall survival and in-hospital mortality in resectable non-small cell lung cancer (NSCLC) patients varies with race. Asian patients have a better overall survival compared with White and Black patients, however, the prognostic factors contributing to these differences are still under studied. The aim of this study was to identify race-specific prognostic factors of overall mortality and in-hospital mortality in resectable NSCLC patients.
Method:
Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims between 1991-2010, 35,461 NSCLC patients who underwent pulmonary resection were extracted. Factors associated with in-hospital mortality and overall mortality stratified by Asian and White were analyzed by multivariable logistic regression analysis and multivariable cox regression analysis, respectively.
Result:
Factors associated with in-hospital mortality in Asian patients were age ≥ 80 years (adjusted odd ratios (OR~adj~)=5.8, 95% Confidence interval (CI)=1.59-21.23), stage III disease (OR~adj~=3.93, 95%CI=1.55-9.96), lower lobe lesion (OR~adj~=3.52, 95%CI=1.54-8.02), pneumonectomy (OR~adj~=11.12, 95%CI=2.61-47.34), postoperative pulmonary complication (OR~adj~=5.39, 95%CI=2.51-11.56), postoperative infections (OR~adj~=28.19, (95%CI=10.62-74.83), and intraoperative complication (OR~adj~=10.87, 95%CI=2.64-44.79). In White patients factors associated with in-hospital mortality were old age, male gender, higher comorbidity index, advanced stage, non-teaching hospital, lower hospital volume, pneumonectomy, preoperative radiotherapy, postoperative and intraoperative complications. Factors associated with overall mortality in Asian patients were age ≥ 80 years (HR~adj~=1.63, 95%CI=1.23-2.16), higher Elixhauser comorbidity index (HR~adj~=1.02, 95%CI=1.01-1.04), lower median income, stage (HR~adj~(95%CI) =1.89(1.41-2.54) for stage II, 2.19(1.69-2.83) for stage III, and 3.85(2.59-5.73) for stage IV versus stage I), non-teaching hospital, and receiving radiotherapy (HR~adj~=1.76,95%CI=1.35-2.30). In White patients, factors associated with overall mortality included old age, male gender, single status, higher comorbidity index and score, lower median income, higher stage, non-squamous cell carcinoma, higher tumor differentiation, location of tumor, lower hospital volume, pneumonectomy, no mediastinal lymph node dissection, and receiving chemotherapy or radiotherapy.
Conclusion:
Race specific differences in number and type of prognostic factors for in-hospital and overall mortality point at biological differences in the tumor as well as differences in treatment.
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MA 18.08 - Assessment of Baseline Symptom Burden in Treatment-Naïve Patients with Lung Cancer (ID 10246)
15:45 - 17:30 | Presenting Author(s): George R. Simon | Author(s): T.R. Mendoza, K. Kehl, O. Bamidele, L.A. Williams, C.S. Cleeland
- Abstract
- Presentation
Background:
While most cancer therapies are associated with toxicities, a major component of cancer treatment is to reduce cancer-related symptoms and impairment of function. Assessing how well this goal is achieved is dependent on accurate assessments of baseline symptoms prior to initiation of therapy. The objectives of this study were to describe the symptom burden of treatment-naïve lung cancer patients and to examine demographic and disease factors that correlate with symptom severity.
Method:
Symptom data from 460 treatment-naïve patients with lung cancer were obtained using the validated MD Anderson Symptom Inventory via a 0-10 numeric rating scale. Descriptive statistics were used to summarize patient demographic and clinical characteristics. Differences in symptom severity, symptom interference and quality of life by disease stage and histology were examined using either t-test or ANOVA. Multiple linear regression analysis was performed using age, gender, tumor stage and histology to determine significant predictors of pain and shortness of breath.
Result:
The most severe symptoms were fatigue, disturbed sleep, distress, pain, shortness of breath, sadness and drowsiness. About 62% of patients had at least one moderate to severe (rated 5 or greater) symptom, while 48% had at least one severe (rated 7 or greater) symptom. Disturbed sleep, distress, shortness of breath, sadness, and drowsiness were reported to be severe by at least 16% of the patients. As expected, patients with advanced stage had significantly more severe symptoms. Patients with small-cell carcinoma reported the most severe pain and shortness of breath. Multiple linear regression analysis showed that stage was a significant predictor of pain severity while controlling for histology, age and gender. Patients with advanced stage had a pain level that was 1.2 higher than patients with early stage disease (95% CI= 0.5 – 1.8, p<0.001. For shortness of breath, both histology and stage were significant predictors of severe levels while controlling for age and gender. Patients with advanced stage had a shortness of breath level that was 0.9 higher than patients with early stage disease (95% CI= 0.4 – 1.6, p<0.001). Patients with small cell carcinoma had a shortness of breath level that was 1.5 higher than those with adenocarcinoma (95% CI= 0.35 – 2.6, p<0.01).
Conclusion:
In conclusion, as much as 62% of treatment-naïve patients with lung cancer reported at least one moderate-to-severe symptoms prior to initiation of cancer therapy. This high burden suggests that symptoms should be assessed routinely and tracked in parallel with cancer treatment.
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MA 18.09 - Enrollment of Minorities, the Elderly, and Women in Lung Cancer Clinical Trials (ID 8406)
15:45 - 17:30 | Presenting Author(s): Narjust Duma | Author(s): C. Yu, J. Paludo, J. Vera Aguilera, M. Gonzalez Velez, C. Haddox, Aaron S. Mansfield, R. Go, Alex Adjei
- Abstract
- Presentation
Background:
Despite multiple efforts led by the National Cancer Institute (NCI) specific patient populations remained underrepresented in cancer clinical trials (CT). Therefore, we determined the representation of minorities, the elderly, and women in lung cancer CT in the past 16 years.
Method:
Clinicaltrials.gov was queried on December 31[st], 2016 for all completed therapeutic lung cancer trials from 2000 to 2016. Trials with recruitment outside of the U.S. were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER cancer prevalence. Geographic location was classified within the 5 major U.S. regions: Northeast, Southeast, Midwest, Northwest and Southwest.
Result:
Out of 320 CT, only 88 trials (27.5%) reported race/ethnicity comprising 11, 723 enrollees. Industry sponsored 65% of the trials. Non-Hispanic whites (NHW) were more likely to be enrolled in CT (EF 2.8%) than African Americans (AA) (EF 1.5%, p<0.001) and Hispanics (EF 2.1% p<0.03). Asian patients were well represented (EF 9.2 %). Distribution by race and sex is described on Table 1. Only 44 (50%) trials divided participants by age (<65 or ≥65 years). The representation of trial participants was heavily skewed towards the younger age group. Median age was 62 years and 8,440 (72%) participants were <65 years of age (p<0.001). Industry sponsored trials were less likely to enroll Hispanic patients than NCI sponsored trials (1.1% vs. 3.8%). African Americans were less likely to be recruited in first line trials compared to NHW (11% vs. 36%, p<0.0001). Underrepresentation of minorities was not affected by recruitment site geographic location.
Conclusion:
NHW were more likely to be enrolled in clinical trials than African American and Hispanics, independent of the recruitment site geographic location. Collaboration between investigators, NCI, industry, and the community is necessary to ensure broad access of unrepresented populations to clinical trials.Race/Ethnicity 2000-2016 Trial Participants n/% Enrollment Fraction % 2013 Lung Cancer Prevalence % Non-Hispanic White 9,350 (79.8) 2.8 82.7 African American 638 (5.4) 1.5 10.6 Hispanic 314 (2.7) 2.1 3.6 Asian/PI 1083 (9.2) 8.7 3.1 Native American 75 (0.6) N/A N/A Other 263 (2.2) Sex Female 4,571 (39) 2.0 55.2 Male 7,152 (61) 3.8 44.8
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MA 18.10 - Discussant - MA 18.06, MA 18.07, MA 18.08, MA 18.09 (ID 10791)
15:45 - 17:30 | Presenting Author(s): Manfred Neuberger
- Abstract
- Presentation
Abstract not provided
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MA 18.11 - High Incidence of Lung Cancer in Early Stage TCC Patients (ID 9292)
15:45 - 17:30 | Presenting Author(s): Yaakov Tolwin | Author(s): I. Nardi-Agmon, E. Rosenbaum, Nir Peled
- Abstract
- Presentation
Background:
In recent years, clinical studies on screening for lung cancer have demonstrated an initial lung cancer detection rate of 0.8-2.2%, with a total of 2.4-4.7% in 34-78 months of follow up. The National Lung Screening Trial (NLST), which compared screening by LDCT to annual chest X-ray, showed a 20% decrease in mortality in the screened population. Transitional cell carcinoma of the bladder (TCC) has a high survival rate, and has similar risk factors to lung cancer. Thus, TCC patients may stand to benefit from lung cancer screening.
Method:
The SEER (Statistics, Epidemiology and End Results) database was used to determine the incidence, Person-years at risk and the average time to diagnosis of lung cancer in patients with localized TCC of the bladder (American Joint Committee on cancer, 6[th] ed., stages 0-1) in years 2000-2013. Cumulative Incidence rates were calculated and stratified by age, sex and county level smoking data.
Result:
Based on 88,564 patients with localized TCC (F:M ratio 1:3.3), the 5 year incidence of lung cancer was 3.16%, and 10 year incidence was 5.85%. among patients over 40 from counties with a high percentage of smokers, the 5 year incidence of lung cancer was 3.46%, and 10 year incidence was 6.64%. The median time until diagnosis of lung cancer was 3.89 years for men and 3.16 years for women for ages 60-79, the age group with the highest incidence. Figure 1
Conclusion:
Incidence of lung cancer is high in localized TCC patients and comparable to results seen in the high risk groups currently being screened. Early stage TCC patients may therefore stand to gain from lung cancer screening, and should be considered as potential screening candidates.
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MA 18.12 - Quality of Data Informing Epidemiological Studies in Patients with Lung Cancer (ID 7550)
15:45 - 17:30 | Presenting Author(s): Marliese Alexander | Author(s): S.M. Evans, R. Wolfe, A. Officer, Rob Stirling, M.P. Macmanus, Ben J Solomon, David L Ball, K. Burbury
- Abstract
- Presentation
Background:
Epidemiological studies commonly use data from clinical (i.e. medical records) and administrative (i.e. claims data) datasets for the purposes of exploratory analyses, as well as clinical and quality reporting, benchmarking, risk adjustment, and machine learning. Validity is contingent on accurate and detailed reporting of data, demanding robust methodological validation.
Method:
Single centre retrospective comparative study assessing completeness and agreement (kappa-statistic (κ)) of data reporting for key prognostic variables across three independent data sources, among patients with lung cancer. The study population was formed by random selection of patients from an Australian single centre prospective study. Prospectively collected research study-data (SD) was extracted, and then compared to data extracted from individual patient medical records (MR) as well as International Classification of Diseases (ICD) coding from administrative data (AD).
Result:
The study population included 10% of patients from an Australian lung cancer cohort (n=111/1090), and represented the overall cohort in terms of patient demographics and disease characteristics. Prognostic data for stage, comorbidities, smoking history, performance status, and weight loss at diagnosis, was reported for >96% of patients in SD. Comparatively, AD did not report any prognostic data for 42% (47/111) of patients treated in ambulatory settings, and indeed when reported was grossly inaccurate. By way of examples, according to AD, 23% of patients had ≥1 comorbidity versus 68% by MR and 64% by SD; 38% had positive smoking history versus 78% by MR and 81% by SD; 2% had respiratory comorbidity versus 28% by MR and 37% by SD. Similar patterns were observed for other comorbid conditions. Complete TNM staging was captured in only 45% of MR at the time of first treatment, although with good concordance with SD (κ=0.9, 95%CI 0.7, 1.0). Equally when factors were documented in MR they were reasonably concordant with SD: smoking status (completeness 96.4%, κ=0.9, 95%CI 0.8, 1.0), performance status (completeness 82.0%, κ=0.5, 95%CI 0.4, 0.7) and weight loss (completeness 71.1%, κ=0.3, 95%CI 0.1, 0.5).
Conclusion:
Poor capture of factors (either omission or inaccuracy) limit the potential contribution of both MR and AD for use in clinical, epidemiological, and machine learning research – particularly when being utilised to derive diagnostic, prognostic and classification systems. Use of this data for purposes other than intended may misinform estimates of comorbidity disease burden and fail to appropriately adjust for competing mortality risks in models that inform outcomes reporting and ensuing policy decisions.
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MA 18.13 - Mutation Profile of EGFR Gene in Chinese Patients with Non-Small-Cell Lung Cancer (NSCLC): An Analysis of 2,666 Cases (ID 8974)
15:45 - 17:30 | Presenting Author(s): Dongmei Lin
- Abstract
- Presentation
Background:
Mutations of epidermal growth factor receptor (EGFR) gene have been proved as the strongest predictor of response to EGFR-tyrosine kinase inhibitor (TKI) treatment in NSCLC. Currently, 7 most common somatic mutations of EGFR have been reported, among which, L858R and exon 19 deletion theoretically confer sensitivity to EGFR TKIs, other primary EGFR mutations may confer resistance. The EGFR mutation profile showed significant geographical differences (about 35% in East-Asia and 10% in Caucasian population) but very limit data have been reported from China. In addition, we carried liquid biopsy and next generation DNA sequencing analysis on 180 samples from NSCLC patients. We hereby reported the mutation profile EGFR gene in a large scale, real world cohort of 2,666 Chinese NSCLC patients.
Method:
From January 2016 to June 2017, 7 primary EGFR mutations (L858R, Exon 19 del, G719X, L861Q, Exon 20 ins, S768I and T790M) were assayed in tumor tissue (paraffin-embedded or fresh) of 2,666 Chinese patients with NSCLC by a commercial TaqMan PCR kit (Human EGFR Gene Mutations Detection Kit（ACCB）). For liquid biopsy analysis, cell-free DNA is extracted from plasma, a panel of 96-targeted genes was assayed, and genomic alterations in cancer-associated somatic variants are analyzed by massively parallel sequencing.
Result:
Among the 2,666, 1,601(45.9%) were female and 1,447(54.1%) were male, 2,446 (91.7%) had adenocarcinoma (ADC) and 220(8.3%) had squamous carcinoma (SC).The median age of patients was 63 yr (range 17yr-91yr). The detailed EGFR mutation profile was shown in Table 1, the overall incidence of EGFR mutation was 1,319(49.5%). Compare to female patients, male patients showed significant lower rate of EGFR mutation (67.2% vs. 34.6%, p<0.01). More than 50% of patients with ADC showed EGFR mutation while the rate was only 10% in patients with SC. Exon 19 del and L858R, 2 markers for potential better response of TKI, account for the vast majority of all the EGFR mutations. We found the mutation profiles from samples analyzed by NGS is similar to those analyzed by PCR method.
Conclusion:
In Chinese NSCLC female patients with lung adenocarcinoma, exon 19 del and L858R represented more than 90% of the total EGFR mutations, thus, for those whose EGFR status was unable to be determined, direct TKI treatment many has an odd of 60% to benefit the patients. About 5% of SC patients also showed exon 19 del and L858R mutation which means they could be subjects for TKI treatment.
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MA 18.14 - Non-Small Cell Lung Cancer (NSCLC) Treatment and Survival in Scandinavia: The SCAN-LEAF Study (ID 9295)
15:45 - 17:30 | Presenting Author(s): Simon Ekman | Author(s): M. Planck, O.T. Brustugun, J. Rockberg, A. Juarez-Garcia, M. Manley Daumont, H. Huang, M. Pereira, J. Svärd, M. Rosenlund, Oana Chirita, L. Jørgensen, Martin Sandelin, J.B. Sørensen
- Abstract
- Presentation
Background:
As the lung cancer treatment landscape evolves, it is important to understand changes in care and outcomes of patients with NSCLC. SCAN-LEAF objectives include describing NSCLC disease, treatments and health outcomes in Scandinavia (Denmark, Norway and Sweden). The present analyses examined treatment proportions and temporal trends in overall survival, drawing on national registry data.
Method:
NSCLC patients diagnosed 2005-2013 (follow-up until 2014) were included in the present analyses of this retrospective longitudinal cohort study. Patient characteristics and treatment described included demographics, disease stage at initial diagnosis [resectable: I-IIIA; locally advanced: IIIA-B (radiation therapy within 3 months); advanced: IIIB (no radiation therapy within 3 months)-IV], histology, non-drug treatment (surgery and radiation: present analyses include Norway and Sweden 2008-2014 only), and survival. Overall survival (OS) (%+95% CI) was calculated 1, 3, and 5 years post-diagnosis, by stage, and by diagnosis year.
Result:
66,012 NSCLC patients were diagnosed during 2005-2013 in Scandinavia (53.6% male, mean age 68.9 years); diagnosis stage: resectable (26%), locally advanced (15%), advanced (59%). In Norway and Sweden, surgery was performed on 58.5%, 9.9% and 1.9% of patients at resectable, locally advanced and advanced stage, respectively; radiation therapy in 28.0%, 58.0% and 30.4%, respectively. 1-yr OS gradually and significantly improved by calendar year of diagnosis for all disease stages. At 3 and 5 years post-diagnosis, OS was positively and significantly associated with calendar year of diagnosis for patients with resectable and locally advanced, but not advanced disease (Table 1).Table 1. Proportion NSCLC patients from Denmark, Norway and Sweden diagnosed during 2005-2013 who survived 1, 3 and 5 years after diagnosis, by stage and calendar year of diagnosis. Stage at diagnosis & Calendar year of diagnosis % survived 1-, 3- and 5-years after NSCLC diagnosis 1-year 3-year 5-year Resectable disease Overall 81.0% (80.4%, 81.6%) 56.8% (55.9%, 57.7%) 43.5% (42.5%, 44.6%) 2005 74.7% (72.5%, 77.0%) 51.0% (48.5%, 53.6%) 40.0% (37.4%, 42.5%) 2006 77.0% (74.8%, 79.2%) 53.3% (50.7%, 55.9%) 42.3% (39.7%, 44.8%) 2007 78.6% (76.6%, 80.7%) 55.0% (52.5%, 57.5%) 43.5% (41.1%, 46.0%) 2008 80.6% (78.6%, 82.5%) 56.4% (53.9%, 58.8%) 44.2% (41.7%, 46.7%) 2009 79.7% (77.7%, 81.7%) 57.4% (55.0%, 59.8%) 45.8% (43.3%, 48.2%) 2010 81.4% (79.6%, 83.2%) 59.1% (56.8%, 61.4%) 2011 83.1% (81.4%, 84.7%) 61.2% (59.0%, 63.4%) 2012 85.5% (84.0%, 87.0%) 2013 84.2% (82.7%, 85.8%) p-value trend <0.0001 <0.0001 0.0008 Locally advanced disease Overall 52.0% (51.0%, 53.0%) 18.4% (17.5%, 19.3%) 10.8% (9.9%, 11.6%) 2005 45.7% (42.4%, 49.0%) 13.9% (11.6%, 16.2%) 7.8% (6.1%, 9.6%) 2006 45.7% (42.3%, 49.1%) 15.4% (12.9%, 17.8%) 10.7% (8.6%, 12.9%) 2007 51.5% (48.2%, 54.7%) 18.6% (16.0%, 21.1%) 11.0% (9.0%, 13.1%) 2008 50.0% (46.7%, 53.3%) 17.0% (14.5%, 19.4%) 10.3% (8.3%, 12.3%) 2009 50.9% (47.8%, 54.0%) 19.8% (17.4%, 22.3%) 12.9% (10.8%, 15.0%) 2010 51.1% (48.1%, 54.1%) 18.9% (16.5%, 21.2%) 2011 55.9% (53.1%, 58.7%) 21.2% (18.9%, 23.5%) 2012 57.0% (54.2%, 59.9%) 2013 56.1% (53.2%, 59.0%) p-value trend <0.0001 <0.0001 0.0021 Advanced disease Overall 26.2% (25.7%, 26.6%) 6.3% (6.0%, 6.6%) 3.4% (3.2%, 3.7%) 2005 24.4% (23.1%, 25.8%) 6.3% (5.5%, 7.0%) 3.5% (2.9%, 4.1%) 2006 24.2% (22.8%, 25.5%) 6.1% (5.4%, 6.9%) 3.4% (2.8%, 4.0%) 2007 25.7% (24.4%, 27.0%) 5.9% (5.2%, 6.6%) 3.1% (2.6%, 3.7%) 2008 25.0% (23.7%, 26.3%) 6.0% (5.3%, 6.7%) 3.3% (2.8%, 3.9%) 2009 26.5% (25.0%, 28.0%) 6.9% (6.0%, 7.8%) 3.9% (3.2%, 4.5%) 2010 26.3% (24.9%, 27.7%) 7.0% (6.2%, 7.8%) 2011 27.4% (26.1%, 28.8%) 6.2% (5.4%, 6.9%) 2012 28.1% (26.7%, 29.5%) 2013 27.9% (26.6%, 29.3%) p-value trend <0.0001 0.2480 0.5359
Conclusion:
These analyses showed modest improvements in survival for patients with earlier stage disease over time. However, the majority of patients were diagnosed with advanced stage disease for which no improvement in temporal trends of survival was found, beyond one year post-diagnosis. This suggests an unmet need for effective treatments still remains, particularly for patients with advanced disease.
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MA 18.15 - Discussant - MA 18.11, MA 18.12, MA 18.13, MA 18.14 (ID 10790)
15:45 - 17:30 | Presenting Author(s): Konstantinos Arnaoutakis
- Abstract
- Presentation
Abstract not provided
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Author of
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MS 14 - QOL Evaluation in Practice from the Viewpoint of Physicians and Nurses (ID 536)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Nursing/Palliative Care/Ethics
- Presentations: 1
- Moderators:Qing Zhou, Beth Eaby-Sandy
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 315
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MS 14.01 - Elements to Reach the Treatment Goal of Palliation (ID 7706)
11:00 - 12:30 | Presenting Author(s): Christian Klaus Manegold
- Abstract
- Presentation
Abstract:
Despite fast growing information of tumor molecular biology, the increase in the therapeutic portfolio, and a significant improvement in diagnostic radiology, treatment of advanced NSCLC in 2017 remains palliative with still no curative perspective for the vast majority of patients. Therefore, the main treatment goals include the change from an acute into a chronic disease, extending survival times as well as improving or just maintaining quality of life. In order to assure an optimal palliation the majority of patients with advanced NSCLC – considering the high age and concomitant comorbidities - frequently may require modifications of the treatment standard. Furthermore, it can also not be ignored that recently approved novel agents and innovative diagnostic technology represent a growing burden of financial toxicity leading to regional differences in the availability of modern therapy and in the access to molecular testing and modern imaging. Nonetheless, treatment algorithms for advanced NSCLC have over the last decade gradually gained in complexity by incorporating a number of diagnostic and therapeutic achievements allowing personalization, individualization, and precision of therapy. Not only patient factors such as performance status (PS), comorbidity, and patients’ treatment expectation must lead to treatment differentiation and modification but also disease characteristics such as tumor stage, tumor load, histological type (squamous vs non–squamous) and the molecular profile of the tumor (mutant vs wild type) influence the process in reaching the goal of optimal sustainable palliation. Other critical elements in realizing personalized therapy and precision medicine within the process of optimal palliation consist in a rational selection of anti-cancer agents (predictive factors, mode of action, toxicity profile) and their appropriate application (single agent, concomitant combinations, drug sequencing) as well as other novel therapeutic actions such as interventional radiology, modern radio therapy, and minimal surgery. Optimal therapeutic management for sustainable palliation should definitely be based on clinically reliable evidence presented by frequently updated treatment recommendations: Today’s treatment algorithm for advanced NSCLC is challenged by a number of newer agents, such as tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors (Table 1),
Table 1 and the incorporation of new treatment strategies such as continuation or switch maintenance therapy (Figure 1).Figure 1 Figure 1 For advanced NSCLC (Figure 2) it is generally accepted that platinum based doubled chemotherapy remains the backbone for the majority of our patients with good PS and this combination therapy should be modified according to feasibility and tolerability, comorbidity, patients’ age over 70 years, PS. Figure 2 Figure 2 For wild type non-squamous NSCLC there is pemetrexed which has been shown to be favorable over older cytotoxic agents if combined with platinum based components. In addition, pemetrexed has also sufficiently demonstrated that if it is continued in case non-progression under four cycles of standard platinum based doublet chemotherapy not containing pemetrexed (switch maintenance) or containing pemetrexed (continuation maintenance) prolongs survival. Another agent, the small molecule and EGFR-tyrosine kinase inhibitor erlotinib also prolongs survival if used in the switch maintenance setting but its benefit depends on the quality of response to the chemotherapy and is restricted to patients which have experienced disease stabilization only. The VEGFR-targeting antibody, bevacizumab, if added to platinum based doublet therapy, specifically to carboplatin/paclitaxel significantly improves response rate, duration of response, progression free survival, as well as overall survival in eligible patients. Human immune checkpoint inhibitor-antibodies inhibiting the PD-1 receptor or PD-1 ligand have recently been integrated into the treatment algorithms of wild type NSCLC. Pembrolizumab is currently the only checkpoint inhibitor approved and recommended for first line therapy in patients with a PD-L1 expression level ≥ 50 % and with negative or unknown EGFR/ALC/ROS1 testing. In wild type squamous NSCLC the given treatment options are still limited and platinum based therapy (no pemetrexed, no bevacizumab) remains the recommended treatment standard. Nonetheless, just recently the EGFR-targeting monoclonal antibody necitumumab has shown to significantly improve survival if combined with the standard doublet regimen cisplatin/gemcitabine in comparison to cisplatin/gemcitabine only and therefore, has just recently approved. Maintenance therapy in squamous tumors with docetaxel or erlotinib (switch) or gemcitabine (continuation) may be justified in some patients even here the statistical evidence is weak. For about 10-30% of NSCLC (in Europe < 15%) non-squamous tumors expressing specific molecular features first-line treatment by genotype has been established. Tumors with sensitizing EGFR mutations have been exposed by gefitinib, erlotinib, and afatinib and have shown to prolong progression free survival over standard platinum based doublet standard therapy. In tumors bearing ALK-/ROS1-gene-rearrangements crizotinib and ceritinib have also shown to prolong progression free survival if compared to platinum based / pemetrexed doublet chemotherapy. Therefore, EGFR-TKI therapy (erlotinib, gefitinib, afatinib) should be prescribed for patient with tumors bearing sensitizing EGFR-mutations and for patients with tumors bearing ALK-/ROS1-gene-rearrangements ALK-/ROS1-targeted therapy (crizotinib, ceritinib) should be prescribed. However, for these patients molecular testing is critical and should be used to select patients for EGFR/ALK/ROS1 targeted therapy. Patients with lung adenocarcinoma should not be excluded from testing on the basis of clinical characteristics (ethnicity, gender, smoking status). Last but not least, second-/subsequent-line therapy is another strong element contributing to sustainable palliation in patients with advanced NSCLC. For tumor without driver mutations agents available before 2014 include docetaxel, pemetrexed (for non-squamous cell tumors only) and erlotinib. In recent years the two antiangiogenic agents nintetanib and ramucirumab (both in combination with docetaxel) and three immune checkpoint inhibitors (nivolumab, pembrolizumab, azetolizumab) have been added to the armentarium to treat patients with advanced non-mutated NSCLC who have progressed on or after first-line therapy (Figure 2). In mutated NSCLC several therapeutic options for second-/subsequent line-therapies are recommended depending on the type of progression and the molecular profile of the tumor. Osimertinib has been just recently approved for EGFRm/790M expressing tumors. For ALK-positive tumors ceritinib, alectinib, and crizotinib can be prescribed. In general, selection of agents for second-/subsequent-line therapies is based on whether the drugs have been used earlier, or toxicity or patients view. References are available by the author.2nd-line Docetaxel, Pemetrexed, EGFR-TKI 1st-line Bevacizumab - non-squamous NSCLC | Ramucirumab / Doc - NSCLC | Bevacizumab/Erl. – EGFRm NSCLC | Nintedanib / Doc - non-squamous | Pemetrexed - non-squamous NSCLC | Nivolumab - NSCLC | Pemetrexed, Erlotinib - maintenance | Osimertinib - EGFRmT790M | Gefitinib, Erlotinib, Afatinib - EGFRm | Crizotinib, Ceritinib – ALK | Necitumumab - squamous NSCLC | Alectinib - ALK | Crizotinib - ALK/ROS | Pembrolizumab – PD-L1-low | Ceritinib – ALK | Atezolizumab - NSCLC | Alectinib -ALK | Pembrolizumab - PD-L1-high
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