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      Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis

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      BMJ : British Medical Journal
      BMJ Publishing Group Ltd.

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          Abstract

          Objective To systematically review the evidence that smoking cessation after diagnosis of a primary lung tumour affects prognosis.

          Design Systematic review with meta-analysis.

          Data sources CINAHL (from 1981), Embase (from 1980), Medline (from 1966), Web of Science (from 1966), CENTRAL (from 1977) to December 2008, and reference lists of included studies.

          Study selection Randomised controlled trials or observational longitudinal studies that measured the effect of quitting smoking after diagnosis of lung cancer on prognostic outcomes, regardless of stage at presentation or tumour histology, were included.

          Data extraction Two researchers independently identified studies for inclusion and extracted data. Estimates were combined by using a random effects model, and the I 2 statistic was used to examine heterogeneity. Life tables were used to model five year survival for early stage non-small cell lung cancer and limited stage small cell lung cancer, using death rates for continuing smokers and quitters obtained from this review.

          Results In 9/10 included studies, most patients studied were diagnosed as having an early stage lung tumour. Continued smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% confidence interval 1.15 to 7.54) and recurrence (1.86, 1.01 to 3.41) in early stage non-small cell lung cancer and of all cause mortality (1.86, 1.33 to 2.59), development of a second primary tumour (4.31, 1.09 to 16.98), and recurrence (1.26, 1.06 to 1.50) in limited stage small cell lung cancer. No study contained data on the effect of quitting smoking on cancer specific mortality or on development of a second primary tumour in non-small cell lung cancer. Life table modelling on the basis of these data estimated 33% five year survival in 65 year old patients with early stage non-small cell lung cancer who continued to smoke compared with 70% in those who quit smoking. In limited stage small cell lung cancer, an estimated 29% of continuing smokers would survive for five years compared with 63% of quitters on the basis of the data from this review.

          Conclusions This review provides preliminary evidence that smoking cessation after diagnosis of early stage lung cancer improves prognostic outcomes. From life table modelling, the estimated number of deaths prevented is larger than would be expected from reduction of cardiorespiratory deaths after smoking cessation, so most of the mortality gain is likely to be due to reduced cancer progression. These findings indicate that offering smoking cessation treatment to patients presenting with early stage lung cancer may be beneficial.

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          Most cited references43

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review.

            As more interventions become available for the treatment of coronary heart disease (CHD), policy makers and health practitioners need to understand the benefits of each intervention, to better determine where to focus resources. This is particularly true when a patient with CHD quits smoking. To conduct a systematic review to determine the magnitude of risk reduction achieved by smoking cessation in patients with CHD. Nine electronic databases were searched from start of database to April 2003, supplemented by cross-checking references, contact with experts, and with large international cohort studies (identified by the Prospective Studies Collaboration). Prospective cohort studies of patients who were diagnosed with CHD were included if they reported all-cause mortality and had at least 2 years of follow-up. Smoking status had to be measured after CHD diagnosis to ascertain quitting. Two reviewers independently assessed studies to determine eligibility, quality assessment of studies, and results, and independently carried out data extraction using a prepiloted, standardized form. From the literature search, 665 publications were screened and 20 studies were included. Results showed a 36% reduction in crude relative risk (RR) of mortality for patients with CHD who quit compared with those who continued smoking (RR, 0.64; 95% confidence interval [CI], 0.58-0.71). Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, type of CHD, and the years in which studies took place. Adjusted risk estimates did not differ substantially from crude estimates. Many studies did not adequately address quality issues, such as control of confounding, and misclassification of smoking status. However, restriction to 6 higher-quality studies had little effect on the estimate (RR, 0.71; 95% CI, 0.65-0.77). Few studies included large numbers of elderly persons, women, ethnic minorities, or patients from developing countries. Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD. This risk reduction appears to be consistent regardless of age, sex, index cardiac event, country, and year of study commencement.
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              Shape of the relapse curve and long-term abstinence among untreated smokers.

              To describe the relapse curve and rate of long-term prolonged abstinence among smokers who try to quit without treatment. Systematic literature review. Cochrane Reviews, Dissertation Abstracts, Excerpt Medica, Medline, Psych Abstracts and US Center for Disease Control databases plus bibliographies of articles and requests of scientists. Prospective studies of self-quitters or studies that included a no-treatment control group. Two reviewers independently extracted data in a non-blind manner. The number of studies was too small and the data too heterogeneous for meta-analysis or other statistical techniques. There is a paucity of studies reporting relapse curves of self-quitters. The existing eight relapse curves from two studies of self-quitters and five no-treatment control groups indicate most relapse occurs in the first 8 days. These relapse curves were heterogeneous even when the final outcome was made similar. In terms of prolonged abstinence rates, a prior summary of 10 self-quitting studies, two other studies of self-quitters and three no-treatment control groups indicate 3-5% of self-quitters achieve prolonged abstinence for 6-12 month after a given quit attempt. More reports of relapse curves of self-quitters are needed. Smoking cessation interventions should focus on the first week of abstinence. Interventions that produce abstinence rates of 5-10% may be effective. Cessation studies should report relapse curves.
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                Author and article information

                Contributors
                Role: research fellow
                Role: senior lecturer, NIHR career scientist
                Role: research associate
                Role: clinical reader, NIHR career scientist
                Journal
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1468-5833
                2010
                2010
                21 January 2010
                : 340
                : b5569
                Affiliations
                [1 ]UK Centre for Tobacco Control Studies, Primary Care Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT
                [2 ]Primary Care Clinical Sciences, University of Birmingham
                Author notes
                Correspondence to: A Parsons  a.c.parsons@ 123456bham.ac.uk
                Article
                para693721
                10.1136/bmj.b5569
                2809841
                20093278
                b4a64882-2131-4a2b-b14f-d897c9b36561
                © Parsons et al 2010

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                Categories
                Research
                Smoking and tobacco
                Epidemiologic studies
                Lung cancer (oncology)
                Lung cancer (respiratory medicine)
                Internet
                Health education
                Health promotion
                Smoking

                Medicine
                Medicine

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