Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, ...microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.
C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.
Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.
ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.
We conducted a randomized trial comparing adjuvant treatment with edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied ...patient- and tumor-specific markers of treatment outcome.
After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of edrecolomab at 28-day intervals or observation without adjuvant therapy.
Final accrual included 1,738 patients; 865 patients received edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival OS, P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer.
Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.
Despite the observation that kidney transplantations from older donors have an increased risk of failure, the percentage of kidney donors 55 years and older has increased. We explored the risk of ...allograft failure in a single transplantation center with older (55-79 years) vs younger (18-54 years) donors.
Retrospective cohort review with a mean follow-up of 32 months.
Academic transplant center.
Consecutive recipients (n = 324) of renal transplants from adult donors.
Patients were divided into 4 groups based on donor status (living or deceased) and donor age (< or =54 or > or =55 years).
Allograft survival and function, incidence of acute rejection.
Recipients of older donor kidneys were significantly older (53.6 vs 43.6 years, P<.001). Seven allografts (12.7%) failed from 55 transplants from donors 55 years and older, compared with 41 allografts (15.2%) from 269 younger donors (P =.63). Renal function was superior following renal transplantation using younger donors (P =.004). However, renal function was acceptable in all groups, with a mean +/- SD serum creatinine level of 1.7 +/- 0.4 mg/dL (150 +/- 35 micro mol/L) among recipients of older donor kidneys. Allograft survival at 1, 2, and 3 years, censored for death with allograft function, did not differ when comparing older vs younger donors.
Most patients receiving allografts from older donors do well. Older donor kidneys provide suitable renal function for many patients on dialysis awaiting transplantation.
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