Mayo Clinic, Rochester, MN
Daniel J. Sargent , Qian Shi , Murray B. Resnick , Stephen Lyle , Michael O. Meyers , Atoussa Goldar-Najafi , Thomas E. Clancy , Sharlene Gill , Jean-Francois Haince , Yves Fradet
Background: Identification of a sensitive and specific prognostic marker would aid in the management of patients (pts) with standard histopathology node negative colon cancer (CC). We conducted a pooled individual pt data analysis to confirm the prognostic value of GCC for disease recurrence in untreated stage II CC. Methods: GCC mRNA was quantified by RT-qPCR using formalin-fixed LN from 310 stage II pts diagnosed from 1991-2006 enrolled in two studies (Sargent 2011 [study1] and Haince 2009 [study2]). Patients were classified by GCC LN ratio (LNR) (high risk: LNR ≥ 0.1; low risk: LNR < 0.1), with LNR defined as number of GCC positive LN divided by number of informative LNs. Clinical outcomes included time to recurrence (TTR), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Stratified log-rank tests and multivariate Cox models assessed the association between clinical outcomes and GCC LN status. Results: The 5-year recurrence rate in study 1 (n=241) was 15.8%, 24.9% in study 2 (n=69). GCC LNR high risk pts had significantly higher risk of TTR, OS, DSS and DFS, which remained after adjusting for age, T stage, grade, number of LNs examined, and presence of lymphovascular invasion (Table). In a secondary analysis of low risk stage II pts (T3, ≥12 LNs examined, and negative surgical margins, n=241), a strong relationship between GCC LNR and each endpoint remained (TTR HR=4.34, 95% CI=2.07 – 9.13, p<0.001). Conclusions: Pts with GCC LNR high risk status have significantly poorer outcomes compared to pts with low risk status, particularly among those traditionally considered to be low risk.
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Hazard ratios comparing high- (LNR ≥ 0.1) and low-risk (LNR < 0.1) groups. | ||||||
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Outcome | GCC risk group | 3-year
event-free rate [95% CI] |
Univariate
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Multivariate
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HR [95% CI] | p | HR [95% CI] | p | |||
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TTR | High | 0.81 [0.74, 0.90] | 2.99 [1.65, 5.42] | <0.001 | 2.55 [1.41, 4.61] | 0.002 |
Low | 0.91 [0.87, 0.95] | - | - | |||
OS | High | 0.85 [0.79, 0.92] | 1.83 [1.17, 2.87] | 0.008 | 1.72 [1.06, 2.80] | 0.028 |
Low | 0.92 [0.88, 0.96] | - | - | |||
DSS | High | 0.81 [0.74, 0.90] | 3.07 [1.73, 5.48] | <0.001 | 2.62 [1.47, 4.67] | 0.001 |
Low | 0.91 [0.87, 0.95] | - | - | |||
DFS | High | 0.75 [0.67, 0.84] | 2.23 [1.51, 3.31] | <0.001 | 2.15 [1.42, 3.25] | <0.001 |
Low | 0.86 [0.82, 0.91] | - | - | |||
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