1. Reducing Tobacco Intake Lowers Risk of Lung Cancer in Heavy Smokers Slideset on: Godtfredsen NS, Prescott E, Osler M. Effect of smoking reduction on lung cancer risk. JAMA. 2005;294:1505-1510.

2. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Background and Rationale  Tobacco implicated in ~ 90% of lung cancer cases, making tobacco-related lung cancer the leading cause of cancer death worldwide  Reducing number of cigarettes smoked per day may decrease tobacco-related harm –Data unclear as to whether reduction in harm affects morbidity or mortality  Present study examined effect of smoking reduction on incidence of lung cancer

3. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Summary of Study Design  Retrospective review of pooled data from 3 large, longitudinal population studies in Denmark –Mean follow-up: 18 years  Primary outcome: number of primary lung cancer cases on follow-up  2 consecutive examinations –Follow-up examination performed within 5-10 years of baseline examination –Examinations conducted between 1964 and 1988

4. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Summary of Study Design (cont’d)  Patients categorized by smoking status –Continued heavy smokers (≥ 15 g/day) –Reducers (≥ 15 g/day at baseline; ≥ 50% reduction at second examination) –Continued light smokers (1-14 g/day) –Exsmokers (no tobacco use at second examination) –Never smokers (no tobacco use at first or second examination)

5. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Baseline Characteristics  Significant differences found between heavy smokers and reducers for all parameters assessed *P value indicates difference between heavy smokers and reducers Parameter Heavy Smokers (n = 7351) Reducers (n = 832) Never Smokers (n = 4006) P Value* Mean age, yrs52.455.154.5<.001 Men, n (%)4896 (66.6)600 (72.1)1351 (33.7).001 Mean tobacco consumption, g/day  At baseline  At follow-up 19.8 20.2 22.2 8.5 0000.001 <.001 Mean pack-years at baseline 31.227.10<.001 Lung cancer cases, n (%)576 (7.8)52 (6.3)28 (0.07)

6. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Main Findings  Reductions in lung cancer risk seen for all populations relative to continued heavy smokers at 2nd observation GroupCrude Hazard Ratio (95% CI)Adjusted Hazard Ratio (95% CI) Heavy smokers1.00 Reducers0.68 (0.50-0.91)0.73 (0.54-0.98) Light smokers0.40 (0.32-0.50)0.44 (0.35-0.56) Quitters0.36 (0.27-0.49)0.50 (0.36-0.69) Exsmokers0.17 (0.13-0.23) Never smokers0.09 (0.06-0.13) CI, confidence interval

7. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Main Findings  Further analyses to compensate for potentially confounding factors did not change findings –Analysis with omission of first 2 years after follow-up –Analysis with omission of participants reporting chronic respiratory conditions or lung disease –Analyses of cigarette smokers only  Independent risk factors for lung cancer according to multivariate analysis included male sex, longer smoking duration, and smoke inhalation

8. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Main Findings  Lung cancer types among current smokers evenly distributed  Tendency toward larger small-cell lung cancer proportion with greater tobacco exposure  Histologic subtypes –Squamous cell carcinoma: 229 cases –Adenocarcinoma: 234 cases –Small-cell lung cancer: 179 cases –Histology not specified: 222 cases

9. clinicaloptions.com/onco Oncology Journal Options Godtfredsen NS, et al. JAMA. 2005;294:1505-1510. Key Conclusions  Among heavy smokers, cutting tobacco consumption by ≥ 50% associated with 27% decrease in lung cancer risk  Lung cancer risk considerably lower among light smokers and participants who quit smoking during study  Reduction in risk may be disproportionately smaller than corresponding reduction in smoking