title: Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer.
abstract: OBJECTIVE
  The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients.
  
  
  METHODS
  The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed.
  
  
  RESULTS
  The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively).
  
  
  CONCLUSIONS
  Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.
authors.affiliation: Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jun Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Yong Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Jun Jeong
authors.initials: JJ
authors.lastname: Choi
authors.forename: Woong Sub
authors.initials: WS
authors.lastname: Koom
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.forename: Nam-Kyu
authors.initials: NK
authors.lastname: Kim
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Ikjae
authors.initials: I
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Keum
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D059186:Chemoradiotherapy, Adjuvant; D051546:Cyclooxygenase 2 / Q000032:analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000401:mortality; D049488:Phosphatidylethanolamine Binding Protein / Q000032:analysis; D011829:Radiation Dosage; D012004:Rectal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D013940:Thymidylate Synthase / Q000032:analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D013940:Thymidylate Synthase; D066246:ErbB Receptors; D005472:Fluorouracil