PURPOSE: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. MATERIALS AND METHODS: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n = 200), NCCTG 86-47-51 (n = 656), and INT 114 (n = 1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. RESULTS:OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. CONCLUSION:Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients.
RCT Entities:
PURPOSE: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. MATERIALS AND METHODS: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n = 200), NCCTG 86-47-51 (n = 656), and INT 114 (n = 1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. RESULTS:OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. CONCLUSION:Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients.
Authors: Young Ju Noh; Won Sik Choi; Jong Hoon Kim; Jin Cheon Kim; Chang Sik Yu; Hee Cheol Kim; Tae Won Kim; Heung Moon Chang; Min Hee Ryu; Seung Do Ahn; Sang-wook Lee; Seong Soo Shin; Jung Eun Lee; Eun Kyung Choi Journal: Cancer Res Treat Date: 2006-02-28 Impact factor: 4.679
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Authors: Leonard L Gunderson; John Milburn Jessup; Daniel J Sargent; Frederick L Greene; Andrew Stewart Journal: J Clin Oncol Date: 2009-11-30 Impact factor: 44.544
Authors: Leonard L Gunderson; John Milburn Jessup; Daniel J Sargent; Frederick L Greene; Andrew K Stewart Journal: J Clin Oncol Date: 2009-11-30 Impact factor: 44.544
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