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Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer.

Authors
 Jun Won Kim  ;  Yong Bae Kim  ;  Jun Jeong Choi  ;  Woong Sub Koom  ;  Hoguen Kim  ;  Nam-Kyu Kim  ;  Joong Bae Ahn  ;  Ikjae Lee  ;  Jae Ho Cho  ;  Ki Chang Keum 
Citation
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, Vol.84(5) : 577-584, 2012 
Journal Title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN
 0360-3016 
Issue Date
2012
MeSH
Adenocarcinoma/chemistry ; Adenocarcinoma/mortality ; Adenocarcinoma/secondary* ; Adenocarcinoma/surgery ; Adenocarcinoma/therapy* ; Adult ; Aged ; Antimetabolites, Antineoplastic/therapeutic use ; Biomarkers, Tumor/analysis* ; Chemoradiotherapy, Adjuvant* ; Cyclooxygenase 2/analysis ; Disease-Free Survival ; Female ; Fluorouracil/therapeutic use ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/chemistry ; Neoplasm Recurrence, Local/mortality ; Phosphatidylethanolamine Binding Protein/analysis ; Radiation Dosage ; Receptor, Epidermal Growth Factor/analysis ; Rectal Neoplasms/chemistry ; Rectal Neoplasms/mortality ; Rectal Neoplasms/pathology ; Rectal Neoplasms/surgery ; Rectal Neoplasms/therapy* ; Thymidylate Synthase/analysis ; Treatment Outcome ; Vascular Endothelial Growth Factor A/analysis
Keywords
Adenocarcinoma/chemistry ; Adenocarcinoma/mortality ; Adenocarcinoma/secondary* ; Adenocarcinoma/surgery ; Adenocarcinoma/therapy* ; Adult ; Aged ; Antimetabolites, Antineoplastic/therapeutic use ; Biomarkers, Tumor/analysis* ; Chemoradiotherapy, Adjuvant* ; Cyclooxygenase 2/analysis ; Disease-Free Survival ; Female ; Fluorouracil/therapeutic use ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/chemistry ; Neoplasm Recurrence, Local/mortality ; Phosphatidylethanolamine Binding Protein/analysis ; Radiation Dosage ; Receptor, Epidermal Growth Factor/analysis ; Rectal Neoplasms/chemistry ; Rectal Neoplasms/mortality ; Rectal Neoplasms/pathology ; Rectal Neoplasms/surgery ; Rectal Neoplasms/therapy* ; Thymidylate Synthase/analysis ; Treatment Outcome ; Vascular Endothelial Growth Factor A/analysis
Abstract
PURPOSE: 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 AND MATERIALS: 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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0360301612033160
DOI
22981710
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Keum, Ki Chang(금기창) ORCID logo https://orcid.org/0000-0003-4123-7998
Koom, Woong Sub(금웅섭) ORCID logo https://orcid.org/0000-0002-9435-7750
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
Kim, Yong Bae(김용배) ORCID logo https://orcid.org/0000-0001-7573-6862
Kim, Jun Won(김준원) ORCID logo https://orcid.org/0000-0003-1358-364X
Kim, Hogeun(김호근)
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Lee, Ik Jae(이익재) ORCID logo https://orcid.org/0000-0001-7165-3373
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90542
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