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Impact of smoking on patients with stage III colon cancer: results from Cancer and Leukemia Group B 89803.

ABSTRACT: Cigarette smoking has been shown to increase the risk of developing colorectal cancer, particularly smoking early in life. Little is known about the impact of tobacco use on colon cancer recurrence among colon cancer survivors.The authors prospectively collected lifetime smoking history from stage III colon cancer patients enrolled in a phase 3 trial via self-report questionnaires during and 6 months after completion of adjuvant chemotherapy. Smoking status was defined as never, current, or past. Lifetime pack-years were defined as number of lifetime packs of cigarettes. Patients were followed for recurrence or death.Data on smoking history were captured on 1045 patients with stage III colon cancer receiving adjuvant therapy (46% never smokers; 44% past; 10% current). The adjusted hazard ratio (HR) for disease-free survival (DFS) was 0.99 (95% confidence interval [CI], 0.70-1.41), 1.17 (95% CI 0.89-1.55), and 1.22 (95% CI 0.92-1.61) for lifetime pack-years 0-10, 10-20, and 20+, respectively, compared with never smoking (P = .16). In a preplanned exploratory analysis of smoking intensity early in life, the adjusted HR for 12+ pack-years before age 30 years for DFS was 1.37 (95% CI, 1.02-1.84) compared with never smoking (P = .04). The adjusted HR for DFS was 1.18 (95% CI, 0.92-1.50) for past smokers and 1.10 (95% CI, 0.73-1.64) for current smokers, compared with never smokers.Total tobacco usage early in life may be an important, independent prognostic factor of cancer recurrences and mortality in patients with stage III colon cancer.

SUBMITTER: McCleary NJ

PROVIDER: S-EPMC2884300 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Impact of smoking on patients with stage III colon cancer: results from Cancer and Leukemia Group B 89803.

McCleary Nadine Jackson NJ Niedzwiecki Donna D Hollis Donna D Saltz Leonard B LB Schaefer Paul P Whittom Renaud R Hantel Alexander A Benson Al A Goldberg Richard R Meyerhardt Jeffrey A JA

Cancer 20100201 4

<h4>Background</h4>Cigarette smoking has been shown to increase the risk of developing colorectal cancer, particularly smoking early in life. Little is known about the impact of tobacco use on colon cancer recurrence among colon cancer survivors.<h4>Methods</h4>The authors prospectively collected lifetime smoking history from stage III colon cancer patients enrolled in a phase 3 trial via self-report questionnaires during and 6 months after completion of adjuvant chemotherapy. Smoking status was ...[more]

PMID: 20052723

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Project description:PurposeTumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results.Patients and methodsTumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis. Tumor mismatch repair deficiency (MMR-D) and BRAF c.1799T?>?A (p.V600E) mutation status were also examined. Relationships between tumor TS, MMR-D, and BRAF mutation status, overall survival (OS), and disease-free survival (DFS) were investigated in the subset of stage III patients.ResultsPatients whose tumors demonstrated high TS expression experienced better treatment outcomes, with DFS hazard ratio (HR)?=?0.67, 95% confidence interval (CI)?=?0.53, 0.84; and OS HR?=?0.68, 95% CI?=?0.53, 0.88, for high versus low TS expression, respectively. No significant interaction between TS expression and stage was observed (DFS: interaction HR?=?0.94; OS: interaction HR?=?0.94). Tumors with high TS expression were more likely to demonstrate MMR-D (22.2% vs. 12.8%; p?=? .0003). Patients whose tumors demonstrated both high TS and MMR-D had a 7-year DFS of 77%, compared with 58% for those whose tumors had low TS and were non-MMR-D (log-rank p?=? .0006). Tumor TS expression did not predict benefit of a particular therapeutic regimen.ConclusionThis large prospective analysis showed that high tumor TS levels were associated with improved DFS and OS following adjuvant therapy for colon cancer, although tumor TS expression did not predict benefit of 5-FU-based chemotherapy. The Oncologist 2017;22:107-114Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility.

Project description:BACKGROUND:The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists' perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer. MATERIALS AND METHODS:A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi-square tests were used to summarize information. RESULTS:Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0-8.5; p < .01 compared with pre-IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients. CONCLUSION:IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk-stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients. IMPLICATIONS FOR PRACTICE:This global survey illustrates that most gastrointestinal medical oncologists now use a risk-stratified approach for determining the duration of adjuvant chemotherapy for stage III colon cancer. Clinicians are five times more likely to choose CAPOX over FOLFOX after the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration results.

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Impact of smoking on patients with stage III colon cancer: results from Cancer and Leukemia Group B 89803.

Publications

Impact of smoking on patients with stage III colon cancer: results from Cancer and Leukemia Group B 89803.

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