title: High-grade acute organ toxicity during preoperative radiochemotherapy as positive predictor for complete histopathologic tumor regression in multimodal treatment of locally advanced rectal cancer.
abstract: OBJECTIVE
  To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer.
  
  
  METHODS
  From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.4 Gy, and either two cycles of 5-fluorouracil (5-FU) or two cycles of 5-FU and oxaliplatin. Toxicity during treatment was monitored weekly, and any toxicity CTC (Common Toxicity Criteria) >or= grade 2 of enteritis, proctitis or cystitis was assessed as high-grade organ toxicity for later analysis. Complete histopathologic tumor regression (TRG4) was defined as the absence of any viable tumor cells.
  
  
  RESULTS
  A significant coherency between high-grade acute organ toxicity and complete histopathologic tumor regression was found, which was independent of other factors like the preoperative chemotherapy schedule. The probability of patients with acute organ toxicity >or= grade 2 to achieve TRG4 after neoadjuvant treatment was more than three times higher than for patients without toxicity (odds ratio: 3.29, 95% confidence interval: [1.01, 10.96]).
  
  
  CONCLUSIONS
  Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors' working group.
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Hendrik Andreas
authors.initials: HA
authors.lastname: Wolff
authors.affiliation: Department of Surgery, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Gaedcke
authors.affiliation: Department of Medical Statistics, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.|Department of Radiotherapy and Radiooncology, Ärztehaus am Diako, Bremen, Germany.
authors.forename: Robert Michael
authors.initials: RM
authors.lastname: Hermann
authors.affiliation: Department of Pathology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Hilka
authors.initials: H
authors.lastname: Rothe
authors.affiliation: Department of Clinical Pharmacology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schirmer
authors.affiliation: Department of Surgery, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Markus Karl Alfred
authors.initials: MKA
authors.lastname: Herrmann
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hennies
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Fränk
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany. hchrist@gwdg.de.|Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Robert-Koch-Str. 40, 37075, Göttingen, Germany. hchrist@gwdg.de.
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003556:Cystitis / Q000209:etiology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004751:Enteritis / Q000209:etiology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D011349:Proctitis / Q000209:etiology*; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D013223:Statistics as Topic
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil