Created by W.Langdon from gp-bibliography.bib Revision:1.4910
METHODS: Archival formalin-fixed, paraffin-embedded (FFPE) primary adenocarcinoma tissues obtained at surgery were retrieved from 74 patients with CRC (15 with stage I disease and 59 with stage II disease) for Training/Test Sets. In addition, FFPE tissues were retrieved from 49 patients with stage I CRC and 215 patients with stage II colon cancer for an External Validation (EV) Set (n=264) from 18 hospitals in 4 countries. No patients had received neoadjuvant/adjuvant therapy. Proprietary genetic programming analysis of expression profiles for 225 prespecified tumour genes was used to create a 36-month recurrence risk signature.
RESULTS: Using reverse transcriptase-polymerase chain reaction, a 5-gene rule correctly classified 62 of 92 recurrent patients and 87 of 172 nonrecurrent patients in the EV Set (sensitivity, 0.67; specificity, 0.51). High-risk patients had a greater probability of 36-month recurrence (42percent) than low-risk patients (26percent; hazard ratio, 1.80; 95percent confidence interval, 1.19-2.71; P=0.007; Cox regression) independent of T-classification, the number of lymph nodes examined, histologic grade/subtype, anatomic location, age, sex, or race. The rule outperformed (P=0.021) current National Comprehensive Cancer Network Guidelines (hazard ratio, 0.897). The same rule also differentiated the risk of recurrence (hazard ratio, 1.63; P=0.031) in a subset of patients from the EV Set who had stage I/II colon cancer only (n=251).
CONCLUSIONS: the 5-gene rule (OncoDefender-CRC) is the first molecular prognostic that has been validated in both stage I CRC and stage II colon cancer. It outperforms standard clinicopathologic prognostic criteria and obviates the need to retrieve >= 12 lymph nodes for accurate prognostication. It identifies those patients most likely to develop recurrent disease within 3 years after curative surgery and, thus, those most likely to benefit from adjuvant treatment.",
Genetic Programming entries for Peter F Lenehan Lisa A Boardman Douglas Riegert-Johnson Giovanni De Petris David W Fry Jeanne Ohrnberger Eugene R Heyman Brigitte Gerard Arpit A Almal William P Worzel