title: Association between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer.
abstract: OBJECTIVE
  Although poorly differentiated cluster has been reported to be a useful grading system for predicting prognosis in colorectal cancer, its relationship to chemotherapy efficacy has not been demonstrated. We aimed to investigate the association between poorly differentiated cluster and the efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer.
  
  
  METHODS
  This retrospective study enrolled 131 patients with stage III colorectal cancer who underwent curative resection: 72 received 5-fluorouracil-based adjuvant chemotherapy (chemotherapy group) and 59 did not (surgery-alone group). Poorly differentiated cluster was defined as a cancer cluster of ≥5 cancer cells without gland-like structure, and was classified into poorly differentiated cluster G1, G2 and G3 according to the number of clusters. The benefit of 5-fluorouracil-based adjuvant chemotherapy was evaluated based on poorly differentiated cluster grade.
  
  
  RESULTS
  Thirty-nine, 40 and 52 patients were classified as poorly differentiated cluster G1, G2 and G3, respectively. Significant differences in the 5-year cumulative recurrence rate and relapse-free survival were observed between poorly differentiated cluster G1/G2 and G3 (26.7% vs. 47.5%, P = 0.010; 66.0% vs. 43.9%, P = 0.004). A comparison of cumulative recurrence rate and relapse-free survival between the chemotherapy and surgery-alone groups showed a significant benefit of adjuvant chemotherapy in poorly differentiated cluster G1/G2 patients (cumulative recurrence rate: 17.4% vs. 37.3%, P = 0.035; relapse-free survival: 79.5% vs. 51.9%, P = 0.002), but not in poorly differentiated cluster G3 patients (cumulative recurrence rate: 48.6% vs. 44.8%, P = 0.885; relapse-free survival: 51.4% vs. 32.7%, P = 0.068).
  
  
  CONCLUSIONS
  In stage III colorectal cancer, poorly differentiated cluster G1/G2 predicts a significant benefit from 5-fluorouracil-based adjuvant chemotherapy, whereas poorly differentiated cluster G3 predicts a poor response to it.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tajima
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kameyama
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Yagi
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Takuma
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Kosugi
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil
keywords: adjuvant chemotherapy; colorectal cancer; poorly differentiated cluster