May 02, 2017
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Smokers with pancreatic cancer at risk for shorter survival

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Patients with pancreatic cancer who smoked near the time of diagnosis were 40% more likely to die after diagnosis than those who never smoked or stopped smoking before diagnosis, according to a prospective study published in Journal of Clinical Oncology.

“Cigarette smoking is not only a risk factor for developing pancreatic cancer, but patients who smoke also have shorter survival times once they are diagnosed with pancreatic cancer,” Brian M. Wolpin, MD, MPH, associate professor of medicine at Harvard Medical School and co-director of the Pancreas and Biliary Tumor Center at Dana-Farber Cancer Institute, told HemOnc Today.

Brian M. Wolpin

Pancreatic cancer is the third leading cause of cancer-related death in the United States, and most patients survive fewer than 12 months after diagnosis.

A prior analysis of 12 prospective cohorts and one case–control study showed current cigarette smokers had an 80% increased risk for pancreatic cancer — which increased with smoking intensity and duration — compared with those who had never smoked. Despite this association, few studies have evaluated smoking’s effect on pancreatic cancer survival.

Wolpin and colleagues prospectively evaluated the association of cigarette smoking with OS among 1,037 patients from two large prospective cohort studies who were diagnosed with pancreatic cancer from 1986 to 2013.

Of these patients, 65.3% had metastatic disease (median OS, 3 months), 19.4% had localized disease (median OS, 19 months) and 15.3% had locally advanced disease (median OS, 9 months).

At the end of follow-up, 1,020 patients (98.4%) had died.

In total, 135 patients were current smokers at the time of diagnosis (mean age, 67.1 years; 71.9% women; 95.6% white; mean BMI, 25.1), 500 smoked before diagnosis (mean age, 72.7 years; 56.2% women; 95.2% white; mean BMI, 26.2), and 402 never smoked (mean age, 72.7 years, 65.4% women; 95.5% white; mean BMI, 26.8).

Researchers estimated HRs for death using Cox proportional hazard models with adjustment for age, sex, race/ethnicity, BMI, diabetes status, diagnosis year and cancer stage.

Patients who currently smoked had a greater risk for mortality than never smokers (HR = 1.37; 95% CI, 1.11-1.69). There was no significant difference in mortality risk between former and never smokers (HR = 0.99; 95% CI, 0.86-1.14).

“We were surprised to find that patients who quit smoking, even in the several years before diagnosis, had no reduction in survival times and did as well as patients who never smoked,” Wolpin said.

The risk increased according to smoking pack-years, from an HR of 1.25 (95% CI, 0.75-2.06) for those with one to 30 pack-years, 1.32 (95% CI, 1-1.75) for those with 31 to 60 pack-years and 1.49 (95% CI, 1.05-2.1) for those with more than 60 pack-years (P for trend = .008).

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Researchers also evaluated the association of prediagnostic plasma cotinine levels — a metabolite of nicotine this is proportional to tobacco smoke exposure — with OS in 485 patients from four prospective U.S. cohorts. Patients with cotinine levels less than 3.1 ng/mL were considered nonsmokers, between 3.1 ng/mL and 20.9 ng/mL light smokers, and greater than 20.9 ng/mL heavy smokers.

Results showed heavy smokers had an increased risk for death (HR = 1.76; 95% CI, 1.23-2.51) compared with nonsmokers. Median OS was 7 months among nonsmokers and 4 months among cotinine-defined heavy smokers.

Researchers noted they used overall mortality as their outcome rather than pancreatic cancer–specific mortality, which could be a limitation of the study.

Further studies are needed to assess the association of smoking with the onset of pancreatic cancer and progression, Wolpin said.

“Smoking cessation is important for many health-related reasons and similarly appears to be an important factor in reducing the number of pancreatic cancer cases and improving the survival times of patients with pancreatic cancer in the United States,” Wolpin said. – by Chuck Gormley

For more information:

Brian M. Wolpin, MD, MPH, can be reached at Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215; email: bwolpin@partners.org.

Disclosure: NCI funded this study. Researchers report no relevant financial disclosures.