Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma.

BACKGROUND: Survivors of Hodgkin's lymphoma are at increased risk for treatment-related subsequent malignant neoplasms. The effect of less toxic treatments, introduced in the late 1980s, on the long-term risk of a second cancer remains unknown. METHODS: We enrolled 3905 persons in the Netherlands who had survived for at least 5 years after the initiation of treatment for Hodgkin's lymphoma. Patients had received treatment between 1965 and 2000, when they were 15 to 50 years of age. We compared the risk of a second cancer among these patients with the risk that was expected on the basis of cancer incidence in the general population. Treatment-specific risks were compared within the cohort. RESULTS: With a median follow-up of 19.1 years, 1055 second cancers were diagnosed in 908 patients, resulting in a standardized incidence ratio (SIR) of 4.6 (95% confidence interval [CI], 4.3 to 4.9) in the study cohort as compared with the general population. The risk was still elevated 35 years or more after treatment (SIR, 3.9; 95% CI, 2.8 to 5.4), and the cumulative incidence of a second cancer in the study cohort at 40 years was 48.5% (95% CI, 45.4 to 51.5). The cumulative incidence of second solid cancers did not differ according to study period (1965-1976, 1977-1988, or 1989-2000) (P=0.71 for heterogeneity). Although the risk of breast cancer was lower among patients who were treated with supradiaphragmatic-field radiotherapy not including the axilla than among those who were exposed to mantle-field irradiation (hazard ratio, 0.37; 95% CI, 0.19 to 0.72), the risk of breast cancer was not lower among patients treated in the 1989-2000 study period than among those treated in the two earlier periods. A cumulative procarbazine dose of 4.3 g or more per square meter of body-surface area (which has been associated with premature menopause) was associated with a significantly lower risk of breast cancer (hazard ratio for the comparison with no chemotherapy, 0.57; 95% CI, 0.39 to 0.84) but a higher risk of gastrointestinal cancer (hazard ratio, 2.70; 95% CI, 1.69 to 4.30). CONCLUSIONS: The risk of second solid cancers did not appear to be lower among patients treated in the most recent calendar period studied (1989-2000) than among those treated in earlier periods. The awareness of an increased risk of second cancer remains crucial for survivors of Hodgkin's lymphoma. (Funded by the Dutch Cancer Society.).

Smoking cessation would substantially reduce the future incidence of pancreatic cancer in the European Union.

OBJECTIVE: Since pancreatic cancer is one of the most rapidly fatal cancers, prevention is of paramount importance to reduce the future burden of this disease. We studied the impact of ceasing smoking on the future incidence of pancreatic cancer in the European Union (EU). METHODS: We developed a computer simulation model, Markov multi-state type, using country-specific published data on population sizes, smoking behaviour, pancreatic cancer incidence and total mortality rates, corresponding relative risks for ex- and current smokers, and estimated probabilities of starting and ceasing smoking (transition rates), with which we refined previously reported preliminary results. We simulated a scenario based on theoretically maximal smoking reduction, a more feasible scenario based on the World Health Organization's 'Health for All' target in which smoking prevalence is reduced to 20% in 2015, and scenarios based on reductions in smoking prevalence in 20 steps of 5% (from 0% to 100% reduction) in 2015. Simulations were based on changes in transition rates for smoking behaviour. We estimated the absolute and relative reduction of pancreatic cancer patients in the EU, for each scenario compared to a reference scenario in which the current transition rates remained unchanged, for the period 1994-2015. RESULTS: Theoretically, if all smokers would quit instantly, the estimated number of new pancreatic cancer patients up to 2015 in the EU could be reduced by 15% (around 150 000 patients). The more feasible scenario would lead to a reduction of almost 29 500 male and 9500 female patients. These results corresponded to a reduction in smoking prevalence with around 45% and 30% among men and women, respectively, in each EU country. CONCLUSION: Giving up smoking would substantially reduce the future incidence of pancreatic cancer. This emphasizes the importance of prevention in the reduction of the future pancreatic cancer burden.

Modelling future mortality reduction through smoking cessation in the European Union.

BACKGROUND: To assess public health relevance of targets on tobacco smoking, information is needed on the decline in future mortality following smoking cessation. WHO's Health for All (HFA) and other targets on tobacco smoking in the European Union (EU) were therefore simulated. METHODS: A computer simulation model, Markov multi-state type, was developed using published age- and sex-specific information on population sizes, smoking prevalences, total and cause-specific mortality rates and corresponding relative risks for ex- and current smokers. The probabilities to start and quit smoking (transition rates) were estimated. Targets on smoking cessation included WHO's HFA target (country-specific smoking prevalence is reduced to 20% by 2015), and a theoretical maximum target (all smokers quit instantly). Simulation of these targets was based on changes in transition rates for smoking behaviour. For each target, the cumulated number of all-cause and cause-specific deaths between 1994 and 2015 was estimated for each EU member state. Then, the absolute and relative reduction in the number of deaths compared to a reference scenario, in which transition rates for smoking behaviour remained constant, were estimated for the EU as a whole. RESULTS: WHO's HFA target was expected to give a total mortality reduction by 2015 of 2.5% (around 1.1 million deaths) among men and 0.8% (almost 350,000 deaths) among women in the EU. Overall, the expected mortality declines in the HFA target were about 40-50% (men) and 30% (women) of the expected declines in the maximum target. The largest impact of the HFA target would be reached for lung cancer mortality. CONCLUSIONS: These results emphasize the need for policymakers in each EU member state to put strong effort into encouraging smokers to quit smoking.

Future burden and costs of smoking-related disease in the Netherlands: a dynamic modeling approach.

OBJECTIVES: In this article, we explore the future health gain of different policy measures to reduce smoking prevalence: health education campaigns specifically aimed at keeping (young) people from starting to smoke, campaigns aimed at persuading smokers to quit, and tax measures. METHODS: We drew up different policy scenarios based on evaluations of several health promotion campaigns. Implementing these into the dynamic multistate models, we simulated smoking prevalence, loss of life-years, and costs for several decades into the next century. RESULTS: In the short run, campaigns aimed at potential "quitters" appear to be most effective in terms of health gain. However, their effect fades away after several decades, while campaigns aimed at young "starters" or tax measures in the end yield a larger and more lasting decrease in smoking attributable disease burden. CONCLUSION: Dynamic modeling is very useful tool in calculating costs and effects of preventive public health measures.