Expression of Hypoxia-inducible Factor 1α Predicts Clinical Outcome after Preoperative Hyperthermo-chemoradiotherapy for Locally Advanced Rectal Cancer
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概要
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Hypoxia-inducible factor 1α (HIF-1α) is an intrinsic marker of tumor hypoxia. It has been considered that hypoxic conditions reduce radiosensitivity, but the role of HIF-1α in patients treated with preoperative therapy for rectal cancer is still unclear. The aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (HCRT) and the prognostic significance of HIF-1α expression in patients with locally advanced rectal cancer. Between 2003 and 2006, 50 patients with histologically proven rectal adenocarcinoma who underwent HCRT followed by surgery were investigated. HIF-1α expression was immunohistochemically evaluated using pre-treatment biopsies. The total radiation dose was 40–50 Gy and chemotherapy consisted of 5-FU and LV administered by continuous infusion on Day 1–5, Day 15–19, and Day 29–33 during radiotherapy. Hyperthermia treatment was performed for once a week for 2–5 sessions. The surgical operation was performed 8 weeks after HCRT and each resected specimen was graded by histological criteria of the Japanese Classification of Colorectal Carcinoma. The effects of HIF-1α on clinical outcomes were analyzed by univariate and multivariate analysis. Positive HIF-1α expression was recognized in 42.0% of samples (21/50). Resected specimens that showed pathological grades 1, 2, and 3 numbered 17, 24, and 9 cases, respectively. There were no significant differences between the HIF-1α-positive group and HIF-1α-negative group for pathological grading and pCR. Overall survival (OS) rate at 3 years in the HIF-1α-negative group was 85.2%, which was significantly better than the 60.6% in the HIF-1α-positive group. Recurrence-free survival (RFS) rate at 3 years in the HIF-1α-negative group was 82.8%, being significantly better than 47.6% in the HIF-1α-positive group. In addition, elevated HIF-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. HIF-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with HCRT.
- 2011-11-16
著者
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ISHIKAWA Hitoshi
Department of Radiation Oncology, Gunma University Graduate school of Medicine
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SUZUKI Yoshiyuki
Department of Radiation Oncology, Gunma University Graduate school of Medicine
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TAKAHASHI Takeo
Department of Radiation Oncology, Gunma University Graduate school of Medicine
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Ohno Tatsuya
放射線医学総合研究所重粒子医科学センター病院
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Ebara Takeshi
Department Of Health Science Of Working Life And Environment Nagoya City University Graduate School
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Nakano T
Centrifuge Project Team Nasda
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Nakano Takashi
Department Of Anatomy Aichi Medical University
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Nakano Takashi
Department Of Radiology And Radiation Oncology Gunma University Graduate School Of Medicine
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SAITOH Jun-ichi
Department of Radiation Oncology, Gunma University Graduate School of Medicine
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Ebara Takeshi
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Ikehira Hiroo
Division Of Advanced Technology For Medical Imaging Research Center Of Charged Particle Technique Na
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Tamaki Tomoaki
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Suzuki Yoshiyuki
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Kuwano Hiroyuki
Department Of General Surgical Science (surgery 1) Gunma University Graduate School Of Medicine
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Taketomi Takahashi
Department Of Diagnostic Radiology And Nuclear Medicine Gunma University Graduate School Of Medicine
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Shioya Mariko
Department Of Anatomy And Cell Biology Gunma University School Of Medicine
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Nonaka Tetsuo
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Nonaka Tetsuo
Department Of Radiology Gunma Cancer Center
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Asao Takayuki
Department Of General Surgical Science (surgery I) Graduate School Of Medicine Gunma University
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Sakurai Hideyuki
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Asao Takayuki
Department Of General Surgical Science Gunma University Graduate School Of Medicine
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Saitoh Jun-ichi
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Tanaka Naritaka
Department Of General Surgical Science (surgery I) Gunma University Graduate School Of Medicine
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Ohno Tatsuya
Department Of Radiation Oncology Graduate School Of Medicine Gunma University
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Nakazawa Tsugio
Department Of Tumor Pathology Gunma University Graduate School Of Medicine
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Suzuki Yoshiyuki
Department Of Cardiovascular Medicine Hokkaido University School Of Medicine
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Ishikawa Hitoshi
Department Of Mechanical Engineering Tokyo University Of Science
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Takahashi Takeo
Department Of Anesthesiology Sapporo Medical College And Hospital
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Takahashi T
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Suzuki Yoshiyuki
Department Of Applied Physics Tohoku University
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Kato Hiroyuki
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Sakurai Hideyuki
Department Of Radiation Oncology Graduate School Of Medicine Gunma University
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Shioya Mariko
Department Of Radiation Oncology Gunma University Graduate School Of Medicine
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Harada Kosaku
Gunma University Heavy Ion Medical Center
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Ishikawa Hitoshi
Department of Electrical Engineering, College of Science and Technology, Nihon University, Chiyoda, Tokyo 101-8308, Japan
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