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Abstract
Tobacco use is the leading preventable cause of death worldwide, responsible for over 5 million deaths per year. By 2030 there will be more than 8 million tobacco-attributable deaths annually, if present trends continue, and 80% of them will occur in low and middle-income countries. Approximately half of regular smokers will die of a tobacco-related disease, losing an average of ten years of life compared to never smokers. Tobacco use is the major cause of lung cancer, increasing the risk 15-20 fold, and accounts a substantial fraction of the burden of tobacco-attributable mortality. In the U.S., for example, lung cancer is responsible for 29% of tobacco-attributable deaths. Lung cancer risk extends beyond tobacco users to nonsmokers who are exposed to secondhand smoke, who have a 30% higher risk of lung cancer than other nonsmokers. Reducing tobacco smoking is central to the prevention and treatment of lung cancer. The risk of lung cancer declines progressively with time after a smoker quits, reaching an asymptote at 15-20 years after quitting. Most cancer prevention efforts focus on preventing lung cancer by promotion smoking cessation among smokers and preventing smoking initiation by youths. A strong evidence base exists to guide efforts to reduce the harms of tobacco use. Offering tobacco cessation treatment is a core component of the World Health Organization’s Framework Convention on Tobacco Control, the world’s first global health treaty. It complements policy efforts such as increasing tobacco excise taxes, expanding smoke-free areas, conducting public education campaigns, and restricting tobacco promotion. However, there is an important gap. Reducing tobacco use among smokers with diagnosed lung cancer has received far less attention in cancer care than it deserves, despite a small but growing body of evidence to indicate that continuing to smoke after a lung cancer diagnosis increases all-cause mortality, impairs the response to treatment and worsens the toxicity of treatment, whether surgery, radiation, or chemotherapy. Stopping smoking also improves lung cancer patients’ quality of life by reducing symptoms such as dyspnea and fatigue. A majority of patients diagnosed with lung cancer try to quit after the diagnosis, and effective treatments are available. However, clinicians caring for smokers with lung cancer often neglect to address this issue and to connect smokers to treatment to help them sustain tobacco abstinence. The randomized controlled clinical trial evidence supporting the efficacy of treatments for tobacco use is strong. Systematic reviews agree that effective smoking cessation treatments exist and help many smokers to quit. Proven treatment methods fall into two major categories: psychosocial counseling (also called behavioral support) and pharmacotherapy. Each of these modalities is effective, but combining behavioral support and pharmacotherapy enhances success because the treatments are complementary. Pharmacotherapy primarily relieves nicotine withdrawal symptoms, while counseling aims to improve a smoker’s motivation and confidence to quit and teaches practical coping skills for quitting. Counseling can be delivered in person or by telephone (either voice or text messaging). The evidence base for the efficacy of delivery via the web or smart phone applications is being developed. Smoking cessation pharmacotherapy approximately doubles the success rate of a quit attempt. Three categories of first-line treatment are approved in the U.S. and many other countries: nicotine replacement therapy (NRT), bupropion (an atypical antidepressant), and varenicline (a selective nicotine receptor partial agonist). NRT, the most widely used product, is available in multiple forms including skin patch, gum, lozenge or sublingual tablet, oral inhaler, mouth spray and nasal spray. Combining NRT products (patch plus a shorter acting form) is the most effective way to administer NRT and is recommended by U.S. and U.K. clinical guidelines. Varenicline, the newest product to market, is effective but enthusiasm has been tempered by post-marketing concerns about psychiatric side effects and a possible increased risk of cardiovascular events. Current evidence does not suggest a large adverse effect but studies are ongoing. Cytisine, a partial nicotinic receptor agonist that is less selective for the α4β2 nicotinic receptor than varenicline, is inexpensive and sold in some Eastern European countries. It showed efficacy for smoking cessation in a recent double-blind randomized controlled trial although quit rates were low. If replicated, its low cost could make pharmacotherapy affordable in settings where cost limits medication availability. Nortriptyline, a tricyclic antidepressant, has evidence of efficacy in systematic reviews but is supported by a smaller body of evidence. No other antidepressant and no anti-anxiety medication has demonstrated efficacy for smoking cessation. To date there are few trials of smoking cessation interventions specifically targeted to patients with cancer. However, there is substantial evidence about what works in ambulatory and inpatient medical practice, and this is likely to be generalizable to lung cancer patients. Physicians who routinely deliver brief advice to quit to all smokers increase smokers’ odds of quitting. Providing a brief counselling intervention during an office visit is more effective than advice alone at promoting smoking cessation. Clinicians in ambulatory practice can promote smoking cessation by encouraging a smoker to make a quit attempt and connecting the smoker to evidence-based medication and behavioural treatments available in the health care system or community. Caring for hospitalized smokers provides another opportunity to encourage smoking cessation. Hospital-initiated smoking cessation counselling interventions increase cessation rates after discharge. A system-wide approach to promoting and supporting smoking cessation should be part of standard care in cancer centers and other sites that deliver health care to cancer patients. This would include the systematic identification and documentation of smoking status throughout cancer treatment, routine and repeated offers of tobacco cessation treatment during cancer treatment, and coordination of care among various types of specialists who deliver the cancer care. In our institution, we conducted a pilot trial in newly diagnosed patients with early stage lung cancer to identify smoking status and routinely offer treatment. We compared 12 weeks of varenicline plus counselling with usual care. At end of treatment, quit rates were higher with treatment (34% vs. 14%), and a full-scale randomized trial is underway.

Abstract
Background The National Lung Screening Trial (NLST) demonstrated that screening with low-dose CT compared to screening with chest radiography reduced lung cancer mortality. Several cost-effectiveness analyses of lung cancer screening have been performed and will be reviewed in the presentation. A team of investigators from the NLST developed detailed data collection instruments to prospectively collect information about the entire screening process and cost expenditures while the trial was ongoing with the specific intention of performing a cost-effectiveness analysis after conclusion of the study. The team has concluded this research and now reports the cost-effectiveness of CT screening within the setting of the NLST. Methods Mean life-years, quality-adjusted life-years (QALYs), and mean costs per person and incremental cost effectiveness ratios for three alternative screening strategies using the societal perspective were estimated. CT screening was compared to chest radiographic and no screening, assuming that chest radiographic screening was ineffective and only contributed costs directly related to screening, not lung cancer treatment. Life-years were based on all observed deaths within the trial and projected survival of those alive at the end. Quality adjustments were derived from a subset of participants selected for quality of life surveys. Costs were based on utilization rates, derived from a subset of participants selected for medical record abstraction, and Medicare reimbursements. Life-years, QALYs, and costs were discounted at 3% per year. Uncertainty was assessed using bootstrap sampling of participants, subset analyses based on age, gender, smoking history, and lung cancer risk, and one-way sensitivity analyses on several assumptions. Results In the base case, the CXR screening strategy was dominated. Compared to no screening, CT screening costs $1441 per person and provided an additional 0.0217 QALYs per person; the incremental cost effectiveness ratio was $67,000 per QALY gained. Conclusions CT screening for lung cancer as performed in the NLST appears to be cost effective under a wide range of assumptions. Whether screening outside the trial will be cost effective will depend on who is selected for screening, how screening is performed, and how screenees are subsequently managed. As the United States Preventive Services Task Force has given a draft recommendation of “B” for lung cancer screening, it will need to be covered without a deductible by insurance companies upon implementation of the Patient Protection and Affordable Care Act. Therefore, appropriate implementation of screening is critical. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.)

Abstract
Staging: Positron emission tomography (PET) using the radiopharmaceutical, 18F-2-deoxy-D-glucose (FDG), a D-glucose analog, is useful in the detection of nodal (N) and extrathoracic metastases (M1b) in patients with non-small cell lung (NSCLC). FDG-PET has a higher sensitivity (83%) and specificity (92%) than CT in the detection of nodal metastases. However, a commonly encountered dilemma occurs when nodal imaging is discordant i.e. in patients with NSCLC and small nodes on CT and a positive PET, the predicted post-test probability of N2 malignancy is 62% and when the nodes are >16-mm and the PET is negative, the post-test probability of N2 malignancy is 21%. When the findings are concordant (enlarged nodes on CT and positive PET) the post-test probability of N2 malignancy is 90%. Accordingly, FDG-PET is usually used to direct invasive nodal staging. Metastatic disease (additional nodule/s in the contralateral lung, pleural nodules, malignant pleural or pericardial effusion (M1a) and extrathoracic metastasis (M1b)) are common in patients with NSCLC at presentation. Whole-body FDG-PET imaging improves the accuracy of staging and has a higher sensitivity and specificity than CT in detecting extrathoracic metastases although many solitary FDG-avid extrathoracic lesions are unrelated to the NSCLC. The American College of Surgeons Oncology Trial reports PET sensitivity, specificity, positive predictive value and negative predictive values of 83%, 90%, 36% and 99%, respectively for M1 disease. Importantly, whole-body PET imaging is useful in the detection of occult extrathoracic metastases in patients considered resectable by standard imaging and clinical evaluation and prevents inappropriate resection in up to 20% of these patients. Response: PET is being evaluated in the assessment of therapeutic response and may allow an early and sensitive assessment of the effectiveness of anticancer chemotherapy as FDG uptake is not only a function of proliferative activity but is also related to viable tumor cell number. FDG-PET/CT can predict early response to therapy in patients with stage IIIB-IV NSCLC who receive standard chemotherapy or molecular-targeted therapy. Early metabolic response (after one cycle of systemic therapy) has a significant correlation with best overall response. FDG-PET has also been reported to be useful in the assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Additionally, in patients with advanced NSCLC, FDG-PET can potentially be useful in identifying a subgroup of patients that would benefit from maintenance treatment after completion of first-line chemotherapy. Furthermore, FDG-PET can be useful in the assessment of early response during radiotherapy with respect to overall survival in patients with NSCLC. While FDG-PET/CT assessment may be useful in the prediction of early treatment response, progression-free survival and overall survival in NSCLC, the response to therapy and survival is multifactorial with stage at presentation, performance status and genomic patterns influencing outcome. It is not certain whether FDG-PET in patients with NSCLC will provide reliable and routinely applicable clinical information in terms of therapeutic response. Restaging: In patients with recurrent malignancy after attempted curative treatment of NSCLC, repeat resection, salvage chemotherapy, or radiotherapy are therapeutic options. FDG-PET can detect local recurrence of tumor after definitive treatment with surgery, chemotherapy, or radiotherapy before conventional imaging and has been reported to have a sensitivity of 98-100% and specificity of 62-92%. In one recent prospective study of patients with NSCLC who had undergone surgical resection, PET was able to detect tumor recurrence (sensitivity 93%, specificity 89%, and accuracy 92%) and predict which patients would benefit most from surgical retreatment. Additionally, in patients with NSCLC treated with radical radiotherapy, FDG-PET performed a median of 70 after completion of radical radiotherapy was useful in the assessment of therapeutic response.