title: Building personalized treatment plans for early-stage colorectal cancer patients.
abstract: We developed a series of models to predict the likelihood of recurrence and the response to chemotherapy for the personalized treatment of stage I and II colorectal cancer patients. A recurrence prediction model was developed from 235 stage I/II patients. The model successfully distinguished between high-risk and low-risk groups, with a hazard ratio of recurrence of 4.66 (p < 0.0001). More importantly, the model was accurate for both stage I (hazard ratio = 5.87, p = 0.0006) and stage II (hazard ratio = 4.30, p < 0.0001) disease. This model performed much better than the Oncotype and ColoPrint commercial services in identifying patients at high risk for stage II recurrence. And unlike the commercial services, the robust model included recurrence prediction for stage I patients. As stage I/II CRC patients usually do not receive chemotherapy, we generated chemotherapy efficacy prediction models with data from 358 stage III patients. The predictions were highly accurate: the hazard ratio of recurrence for responders vs. non-responders was 4.13 for those treated with FOLFOX (p < 0.0001), and 3.16 (p = 0.0012) for those treated with fluorouracil. We have thus created a prognostic model that accurately identifies patients at high risk for recurrence, and the first accurate chemotherapy efficacy prediction model for individual patients. In the future, complete personalized treatment plans for stage I/II patients may be developed if the drug prediction models generated from stage III patients are verified to be effective for stage I and II patients in prospective studies.
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Hung-Hsin
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Auspex Diagnostics, Taiwan.
authors.forename: Nien-Chih
authors.initials: NC
authors.lastname: Wei
authors.affiliation: Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Yuan-Tsu
authors.initials: YT
authors.lastname: Lan
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Shin-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Huann-Sheng
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Wei-Shone
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Lin
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Jen-Kou
authors.initials: JK
authors.lastname: Lin
authors.affiliation: Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D057285:Precision Medicine / Q000379:methods*; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity
keywords: colorectal cancer; drug efficacy; microarray; personalized treatment; recurrence