Kimura K, Beppu N, Doi H, Kataoka K, Yamano T, Uchino M, Ikeda M, Ikeuchi H, Tomita N. Impact of preoperative chemoradiotherapy using concurrent S-1 and CPT-11 on long-term clinical outcomes in locally advanced rectal cancer. World J Gastrointest Oncol 2020; 12(3): 311-322 [PMID: 32206181 DOI: 10.4251/wjgo.v12.i3.311]
Corresponding Author of This Article
Kei Kimura, MD, PhD, Assistant Professor, Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. k-kimura@hyo-med.ac.jp
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
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Kimura K, Beppu N, Doi H, Kataoka K, Yamano T, Uchino M, Ikeda M, Ikeuchi H, Tomita N. Impact of preoperative chemoradiotherapy using concurrent S-1 and CPT-11 on long-term clinical outcomes in locally advanced rectal cancer. World J Gastrointest Oncol 2020; 12(3): 311-322 [PMID: 32206181 DOI: 10.4251/wjgo.v12.i3.311]
Kei Kimura, Naohito Beppu, Kozo Kataoka, Tomoki Yamano, Masataka Ikeda, Naohiro Tomita, Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Hiroshi Doi, Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Hiroshi Doi, Department of Radiation Oncology, Kindai University Faculty of Medicine, Sayama, Osaka 589-8511, Japan
Motoi Uchino, Hiroki Ikeuchi, Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Author contributions: All authors helped to perform the research; Kimura K manuscript writing, performing procedures and data analysis; Beppu N contributed to manuscript writing, drafting conception and design, performing experiments, and data analysis; Doi H, Kataoka K, Yamano T, Uchino M, Ikeda M, Ikeuchi H and Tomita N contributed to writing of the manuscript.
Institutional review board statement: The protocol was approved by the Institutional Review Board at Hyogo College of Medicine, Japan (No.2756).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Corresponding author: Kei Kimura, MD, PhD, Assistant Professor, Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. k-kimura@hyo-med.ac.jp
Received: September 27, 2019 Peer-review started: September 27, 2019 First decision: October 18, 2019 Revised: December 8, 2019 Accepted: December 23, 2019 Article in press: December 23, 2019 Published online: March 15, 2020 Processing time: 166 Days and 21 Hours
ARTICLE HIGHLIGHTS
Research background
Prospective studies have investigated the optimal treatment strategies for management of locally advanced rectal cancer, and have concluded that preoperative 5-fluorouracil-based chemoradiotherapy (CRT) at 45–50.4 Gy is a standard treatment. However, local recurrence rate remains about 10%; mainly for highly advanced cases.
Research motivation
Multidisciplinary treatments were planned to overcome highly advanced rectal cancer, such as extended surgery, higher radiation doses, and concurrent use of second drugs, such as oxaliplatin or CPT-11.
Research objectives
The aim of this study was to investigate the safety, therapeutic effect, and outcome of preoperative CRT using S-1 plus irinotecan for locally advanced lower rectal cancer.
Research methods
Between 2009 and 2016, 82 patients underwent total mesorectal excision after preoperative CRT. Preoperative CRT consisted of S-1 (80 mg/m2/d), CPT-11 (60 mg/m2/d), and radiation (total 45 Gy). The median follow-up was 51 months (range: 17-116 mo).
Research results
This regimen was well tolerated in terms of toxicity. Associations between toxicity/feasibility and UGT1A1 polymorphisms were investigated. Compared with patients with wild-type UGT1A1, those with mutant type had more Grade 3 or 4 hematological toxicity (P < 0.05). With regard to oncological outcome, mesorectal fascia invasion and extramural vascular invasion were associated with poor relapse-free survival for locally advanced rectal cancer. However, Cox regression analysis did not detect any risk factors for local recurrence-free survival.
Research conclusions
This regimen had favorable oncological outcomes for highly advanced rectal cancer.
Research perspectives
This was a small retrospective study performed in a single institution. A randomized multicenter study is needed to investigate the influence of dose setting by UGT1A1 polymorphism for preoperative CRT using irinotecan.
