Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

The Outer Solar Systems Origins Survey. I. Design and First-quarter Discoveries

We report the discovery, tracking, and detection circumstances for 85 trans-Neptunian objects (TNOs) from the first 42 deg2 of the Outer Solar System Origins Survey. This ongoing r-band solar system survey uses the 0.9 deg2 field of view MegaPrime camera on the 3.6 m Canada–France–Hawaii Telescope. Our orbital elements for these TNOs are precise to a fractional semimajor axis uncertainty <0.1%. We achieve this precision in just two oppositions, as compared to the normal three to five oppositions, via a dense observing cadence and innovative astrometric technique. These discoveries are free of ephemeris bias, a first for large trans-Neptunian surveys. We also provide the necessary information to enable models of TNO orbital distributions to be tested against our TNO sample. We confirm the existence of a cold "kernel" of objects within the main cold classical Kuiper Belt and infer the existence of an extension of the "stirred" cold classical Kuiper Belt to at least several au beyond the 2:1 mean motion resonance with Neptune. We find that the population model of Petit et al. remains a plausible representation of the Kuiper Belt. The full survey, to be completed in 2017, will provide an exquisitely characterized sample of important resonant TNO populations, ideal for testing models of giant planet migration during the early history of the solar system.