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Medline ® Abstract for Reference 98

of 'Adjuvant chemotherapy for resected stage II colon cancer'

Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study.
Kim GP, Colangelo LH, Wieand HS, Paik S, Kirsch IR, Wolmark N, Allegra CJ, National Cancer Institute
J Clin Oncol. 2007;25(7):767.
PURPOSE: The role of high-degree microsatellite instability (MSI-H) as a marker to predict benefit from adjuvant chemotherapy remains unclear.
PATIENTS AND METHODS: To help define its impact, we conducted an analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) patients who were randomly assigned to a surgery-alone group (untreated cohort) and patients assigned to an adjuvant fluorouracil (FU) -treated group (treated cohort). MSI-H and other potential markers were assessed (TGF-BRII, p53, thymidylate synthase, and Ki67).
RESULTS: In all, 98 (18.1%) of 542 patients exhibited MSI-H, and there was a strong inverse relationship between MSI-H and mutant p53 status (P<.001). The prognostic analyses showed increased recurrence-free survival (RFS) for MSI-H patients versus MSS/MSI-L patients (P = .10), but showed no difference in overall survival (OS; P = .67). There was a potential interaction between MSI-Hand mutant p53 in terms of improved RFS (P = .03). In the predictive marker analysis, we observed no interaction between MSI status and treatment for either RFS (P = .68) or OS (P = .62). Hazard ratios (HR) for RFS for MSI-H versus MSS/MSI-L patients were 0.77 (95% CI, 0.40 to 1.48) in the untreated-patients group and 0.60 (95% CI, 0.30 to 1.19) in the treated-patients group. HRs for OS were 0.82 (95% CI, 0.44 to 1.51) and 1.02 (95% CI, 0.56 to 1.85) for the respective groups. There was a trend toward improved RFS in patients with MSI-H and mutant p53.
CONCLUSION: These results do not support the use of MSI-H as a predictive marker of chemotherapy benefit.
National Surgical Adjuvant Breast and Bowel Project (NSABP) Operations and Biostatistical Centers, Mayo Clinic, Jacksonville, FL 32224, USA. kim.george@mayo.edu