NSABP, NRG Oncology and the University of Pittsburgh, Pittsburgh, PA
Greg Yothers , Alan P. Venook , Takeharu Yamanaka , Yan Lin , Michael Crager , Calvin Y. Chao , Frederick L Baehner , Takayuki Yoshino
Background: The 12-gene Oncotype DX Colon Recurrence Score assay is a clinically validated genomic assay that evaluates recurrence risks in stage II and stage III colon cancer patients independent of clinical-pathologic features. Improved colon cancer care has reduced recurrence rates since the late 1990’s. Methods: Pre-specified patient-specific meta-analysis methods were used to estimate 1-, 3- and 5-year recurrence risk combining the 12-gene colon recurrence score (RS) validation studies CALGB 9581, NSABP C-07 and SUNRISE. Cox models had effects for RS result, number of nodes examined (<12 or ≥ 12), T-stage, MMR status, and stage (II, IIIAB or IIIC). Baseline cumulative hazard estimates used the latest two studies to reflect current medical practice. Estimates for surgery, surgery+5FU and surgery+5FU+oxaliplatin treatment were provided by integrating stage-specific 5FU hazard ratios from a meta-analysis of the QUASAR study (2007) and a pooled analysis of NSABP studies (Wilkinson 2010), and oxaliplatin treatment effect estimates from NSABP C-07. Recurrence risk with 5FU alone was not estimated for MMR-deficient patients due to expected lack of 5FU efficacy in these patients (Sargent 2010). Results: In the overall population of 2,179 patients, 55%, 32% and 13% were Stage II, IIIA/B and IIIC, 63% had ≥12 nodes examined, 90% were T3, and 88% were MMR proficient. Median RS result was 31 (IQR 23–39). RS result and each clinical-pathologic factor contributed independent prognostic information (meta-analysis Wald tests, all p<.001). Risk estimates are generally lower than previous RS report risk estimates. For patients with pathological stage II, T3, MMR-proficient tumors with ≥12 nodes examined, approximately 40% are expected to have 5-year recurrence risk ≤10% with surgery alone based on the distribution of RS results. The table shows example 5-year recurrence risk estimates for specific RS results and clinical-pathologic characteristics. Conclusions: The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.
Example 5-year recurrence risk estimates (95% confidence intervals). | |||||||
---|---|---|---|---|---|---|---|
T-stage | Nodes ex. | MMR status | Stage | RS result | Surgery alone | Surgery+5FU | Surgery+5FU+oxali |
T3 | ≥ 12 | Proficient | II | 10 | 7% (5%, 9%) | 5% (4%, 7%) | 4% (3%, 6%) |
30 | 10% (8%, 13%) | 8% (6%, 10%) | 7% (5%, 9%) | ||||
55 | 17% (13%, 22%) | 13% (10%, 18%) | 11% (7%, 15%) | ||||
Proficient | IIIAB | 10 | 15% (11%, 20%) | 9% (7%, 13%) | 8% (5%, 11%) | ||
30 | 22% (17%, 29%) | 15% (11%, 19%) | 12% (8%, 17%) | ||||
55 | 34% (26%, 44%) | 23% (17%, 31%) | 19% (13%, 27%) | ||||
Deficient | IIIAB | 10 | 9% (5%, 13%) | − | 4% (3%, 8%) | ||
30 | 13% (8%, 20%) | − | 7% (4%, 11%) | ||||
55 | 20% (13%, 31%) | − | 11% (6%, 18%) |
56% of patients in the meta-analysis population were T3 with ≥12 nodes examined.
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