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Predicting the pathologic response of locally advanced rectal cancer to neoadjuvant concurrent chemoradiation using enzyme linked immunosorbent assays (ELISAs) for biomarkers

 Hong In Yoon  ;  Woong Sub Koom  ;  Yong Bae Kim  ;  Byung Soh Min  ;  Kang Young Lee  ;  Nam Kyu Kim  ;  Sang Joon Shin  ;  Joong Bae Ahn  ;  Ki Chang Keum 
 Journal of Cancer Research and Clinical Oncology, Vol.140(3) : 399-409, 2014 
Journal Title
 Journal of Cancer Research and Clinical Oncology 
Issue Date
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Biomarkers, Tumor/blood* ; Carcinoembryonic Antigen/blood ; Chemoradiotherapy, Adjuvant/adverse effects ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy/methods* ; Neoplasm Staging ; Predictive Value of Tests ; Prospective Studies ; Receptor, Epidermal Growth Factor/blood ; Receptors, Urokinase Plasminogen Activator/blood ; Rectal Neoplasms/blood ; Rectal Neoplasms/pathology* ; Rectal Neoplasms/therapy* ; Tissue Inhibitor of Metalloproteinase-1/blood* ; Treatment Outcome ; Vascular Endothelial Growth Factor A/blood
Rectal neoplasms ; Predictive biological markers ; Neoadjuvant chemoradiotherapy ; Tissue inhibitor of metalloproteinase-1 ; Pathologic response
PURPOSE: To investigate the role of biomarkers including serum tissue inhibitor of metalloproteinases-1 (TIMP-1), urokinase plasminogen activator receptor, vascular endothelial growth factor, and epidermal growth factor receptor in predicting pathologic response to neoadjuvant chemoradiation (NACRT) for rectal cancer. METHODS: Between 2007 and 2009, 50 clinical TNM stage II or III patients were analyzed in this prospective study. Pre- and post-NACRT serum levels of biomarkers were assessed using ELISAs. The primary and secondary endpoints were pathologic complete response (pCR) and Mandard regression grade (MRG). RESULTS: The pCR was reported in 5 patients (10.0%). According to the MRG, fifteen patients (30.0%) were divided into group A (Grade I-II), the others in group B (Grade III-V). On univariate analysis, post-NACRT TIMP-1 showed notable significance with pCR (P = 0.092) and significant correlation with MRG group A (P = 0.003). Post-NACRT TIMP-1 ≤ 204.5 ng/mL as cut-off value by ROC curve was associated with more pCR and MRG group A patients (P = 0.016 and 0.002). Interval between NACRT and surgery was related to pCR with approached trend levels of significance (P = 0.05) and to MRG group A significantly on univariate analysis of clinical factors (P = 0.031). On multivariate analysis, post-NACRT TIMP-1 was not significantly related to pCR (P = 0.187), while it was significantly associated with MRG (P = 0.009). Among clinical responders, post-NACRT TIMP-1 level ≤ 204.5 ng/mL was significantly associated with pCR (P = 0.021) and MRG group A (P = 0.003). CONCLUSIONS: Post-NACRT serum TIMP-1 could be used as a predictive marker of pathologic response to NACRT in rectal cancer, even in patients with clinical response.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 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
Min, Byung Soh(민병소) ORCID logo https://orcid.org/0000-0003-0180-8565
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Lee, Kang Young(이강영)
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