title: Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.
abstract: OBJECTIVE
  We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT).
  
  
  METHODS
  TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system.
  
  
  RESULTS
  TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS.
  
  
  CONCLUSIONS
  In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.
authors.affiliation: Department of Radiation Therapy, University of Erlangen, Universitätsstr 27, D-91054 Erlangen, Germany. claus.roedel@strahlen.med.uni-erlangen.de
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Thomas
authors.initials: T
authors.lastname: Papadoupolos
authors.forename: Laszlo
authors.initials: L
authors.lastname: Füzesi
authors.forename: Martin
authors.initials: M
authors.lastname: Klimpfinger
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Raab
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D002288:Adenocarcinoma, Mucinous / Q000473:pathology / Q000628:therapy; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology / Q000628:therapy; D018279:Carcinoma, Signet Ring Cell / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil