TY - JOUR
T1 - Associations between cigarette smoking status and colon cancer prognosis among participants in North Central Cancer Treatment Group Phase III Trial N0147
AU - Phipps, Amanda I.
AU - Shi, Qian
AU - Newcomb, Polly A.
AU - Nelson, Garth D.
AU - Sargent, Daniel J.
AU - Alberts, Steven R.
AU - Limburg, Paul J.
N1 - Funding Information:
Supported by Grants No. R25 CA94880 and K05 CA152715 from the National Cancer Institute, National Institutes of Health, No. CA025224 from the North Central Cancer Treatment Group, and No. CA33601 from the Alliance Statistics and Data Center.
Publisher Copyright:
© 2013 by American Society of Clinical Oncology.
PY - 2013/6/1
Y1 - 2013/6/1
N2 - Purpose: By 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: Compared with never-smokers, ever smokers experienced significantly shorter DFS (3-year DFS proportion: 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.
AB - Purpose: By 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: Compared with never-smokers, ever smokers experienced significantly shorter DFS (3-year DFS proportion: 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.
UR - http://www.scopus.com/inward/record.url?scp=84880726087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880726087&partnerID=8YFLogxK
U2 - 10.1200/JCO.2012.46.2457
DO - 10.1200/JCO.2012.46.2457
M3 - Article
C2 - 23547084
AN - SCOPUS:84880726087
SN - 0732-183X
VL - 31
SP - 2016
EP - 2023
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 16
ER -