title: Preoperative chemotherapy and radiotherapy for locally advanced rectal cancer.
abstract: BACKGROUND
  The adjuvant treatment of rectal cancer is a rapidly evolving field. The standard approach is a combination of chemotherapy and radiotherapy, with the optimal treatment combination and sequencing yet to be determined. Here, we report our early experience of preoperative chemotherapy and radiotherapy (CRT) in locally advanced rectal cancer at Radiation Oncology Victoria to determine its efficacy and the rate of sphincter preservation.
  
  
  METHODS
  Sixty-nine patients (46 men and 23 women) with locally advanced rectal cancer (T3-4 or N1) were treated with preoperative CRT followed by surgical resection of disease. Chemotherapy consisted of either bolus or continuous venous infusion of 5-fluorouracil (5-FU). Radiotherapy to a dose of 45 Gy was delivered to the pelvis followed by a boost of 5.4-14.4 Gy in the majority of patients. Surgical resection was carried out 4-8 weeks following completion of preoperative CRT. Univariate and multivariate analyses were performed to examine variables that may influence local recurrence and overall survival rates.
  
  
  RESULTS
  All patients underwent a complete macroscopic resection, including the three patients that had unrecognized distant metastases discovered at the time of operation. Only two patients had microscopic residual disease. Sphincter preservation was achieved in 16 of 25 patients who were thought to require an abdominoperineal resection. Tumour and/or nodal downstaging were achieved in 47 patients (68%), with a pathological complete response in 12 (17%). At a median follow up of 29 months post-surgery, five patients (7.2%) have developed a local recurrence. Overall 21 patients (30%) have progressed and 12 (18%) have died. Treatment-related toxicity was acceptable and there was no treatment-related mortality. There was no significant relationship found between the pathological response to treatment and any clinical endpoint.
  
  
  CONCLUSIONS
  Our results confirm the high response rates and acceptable toxicity of preoperative treatment. Further studies are required to better define the impact of preoperative chemotherapy and radiotherapy on long-term outcomes.
authors.affiliation: Radiation Oncology Victoria, Royal Milbourne Hospital, Melbourne, Victoria, Australia. mchao@radoncvic.com.au
authors.forename: Michael
authors.initials: M
authors.lastname: Chao
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
authors.forename: Joe
authors.initials: J
authors.lastname: Tjandra
authors.forename: Mark
authors.initials: M
authors.lastname: Cullinan
authors.forename: Stephen
authors.initials: S
authors.lastname: McLaughlin
authors.forename: Ian
authors.initials: I
authors.lastname: Faragher
authors.forename: Iain
authors.initials: I
authors.lastname: Skinner
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011183:Postoperative Complications; D011300:Preoperative Care; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil