Title |
Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer
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Published in |
New England Journal of Medicine, July 2003
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DOI | 10.1056/nejmoa022289 |
Pubmed ID | |
Authors |
Christine M. Ribic, Daniel J. Sargent, Malcolm J. Moore, Stephen N. Thibodeau, Amy J. French, Richard M. Goldberg, Stanley R. Hamilton, Pierre Laurent-Puig, Robert Gryfe, Lois E. Shepherd, Dongsheng Tu, Mark Redston, Steven Gallinger |
Abstract |
Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer. Tumor specimens were collected from patients with colon cancer who were enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy. Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers. Of 570 tissue specimens, 95 (16.7 percent) exhibited high-frequency microsatellite instability. Among 287 patients who did not receive adjuvant therapy, those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004). Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). The benefit of treatment differed significantly according to the microsatellite-instability status (P=0.01). Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability, according to a multivariate analysis adjusted for stage and grade (hazard ratio for death, 0.72 [95 percent confidence interval, 0.53 to 0.99]; P=0.04). By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability. Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Italy | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | <1% |
Italy | 1 | <1% |
Hong Kong | 1 | <1% |
France | 1 | <1% |
Brazil | 1 | <1% |
South Africa | 1 | <1% |
Finland | 1 | <1% |
Austria | 1 | <1% |
Canada | 1 | <1% |
Other | 3 | <1% |
Unknown | 485 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 82 | 16% |
Researcher | 69 | 14% |
Student > Master | 64 | 13% |
Student > Bachelor | 46 | 9% |
Student > Postgraduate | 42 | 8% |
Other | 114 | 23% |
Unknown | 81 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 243 | 49% |
Agricultural and Biological Sciences | 57 | 11% |
Biochemistry, Genetics and Molecular Biology | 57 | 11% |
Immunology and Microbiology | 10 | 2% |
Nursing and Health Professions | 8 | 2% |
Other | 22 | 4% |
Unknown | 101 | 20% |