Phipps AI, Shi Q, Newcomb PA, Nelson GD, Sargent DJ, Alberts SR, Limburg PJAssociations between cigarette smoking status and colon cancer prognosis among participants in North Central Cancer Treatment Group Phase III Trial N0147. J Clin Oncol 31(16): 2016-2023

Amanda I. Phipps, Polly A. Newcomb, Fred Hutchinson Cancer Research Center, Seattle, WA
Journal of Clinical Oncology (Impact Factor: 18.43). 04/2013; 31(16). DOI: 10.1200/JCO.2012.46.2457
Source: PubMed


PURPOSEBy using data from North Central Cancer Treatment Group Phase III Trial N0147, a randomized adjuvant trial of patients with stage III colon cancer, we assessed the relationship between smoking and cancer outcomes, disease-free survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by patient and tumor characteristics. PATIENTS AND METHODS
Before random assignment to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus cetuximab, 1,968 participants completed a questionnaire on smoking history and other risk factors. Cox models assessed the association between smoking history and the primary trial outcome of DFS (ie, time to recurrence or death), as well as TTR, adjusting for other clinical and patient factors. The median follow-up was 3.5 years among patients who did not experience events. RESULTS: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to 1.49). There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95% CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by KRAS mutation status was not statistically significant (P = .07). Associations were comparable in analyses of TTR. CONCLUSION
Overall, smoking was significantly associated with shorter DFS and TTR in patients with colon cancer. These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer.

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    • "Our finding of increased mortality in colorectal cancer patients who are current smokers is consistent with some (Munro et al, 2006; Phipps et al, 2011, 2013), but not all (Yu et al, 1997; Park et al, 2006; McCleary et al, 2010; Nordenvall et al, 2013), previous research on this topic. Two studies have found that colon/colorectal cancer patients who were current smokers had poorer survival than those who were non-smokers (Munro et al, 2006; Phipps et al, 2013), whereas another study found that colon cancer-specific mortality, but not rectal cancer-specific mortality, was higher in current smokers than in never or former smokers (Phipps et al, 2011). The remaining four studies found no association between current smoking and survival in colorectal cancer patients (Yu et al, 1997; Park et al, 2006; McCleary et al, 2010; Nordenvall et al, 2013). "
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