title: Radio-chemotherapy as a preoperative treatment for advanced rectal cancer. Evaluation of down-staging and morbidity.
abstract: BACKGROUND
  The standard therapy for patients with clinically resectable rectal cancer is generally considered to be surgery. If the patient is diagnosed with advanced disease, postoperative radio-chemotherapy (RCT) is usually recommended. In our study we aimed to investigate and analyze the effectiveness and toxicity of preoperative pelvic radiotherapy in combination with 5-fluorouracil (5-FU) in locally advanced rectal cancer.
  
  
  METHODS
  From June 1999 to September 2001 we evaluated 50 consecutive patients [37 male and 13 female; average age 65.1 (range 46-79.5) years] with locally advanced rectal carcinoma. 32 patients were staged as uT3, 14 as uT4, and 4 as uT2. Regarding N-staging, 22 patients were diagnosed as uN0. 2 patients had distant metastases, with liver metastases in both instances. Conformal irradiation was performed with a box technique (4-field technique) with a dose of 45 Gy (5 x 1.8 Gy per week for a total of 25 sessions). From days 1-5 and 29-33, all patients received 5-FU (500 mg/m(2 ) per day, as a continuous i.v. injection).
  
  
  RESULTS
  Remission was observed in 28 patients (56%), with down-staging of at least one T-stage. A better success rate was achieved for patients with deep-seated tumors (64% of the patients in this group). Complete remission was observed in 4 patients (8.0%) and progression in 3 (6.0%). 15 patients had no detectable change in tumor staging (30.0%). A surgical R0 resection could be achieved in 43 patients, an R1 resection (minimal margin) in 7. Side effects and toxicity (common toxicity criteria) of RCT included grade I-II dysuria in 5 patients (10%), grade I-II diarrhea in 20 patients (40%), and severe diarrhea in 2 patients (4.0%). Grade I-II skin reaction was noticed in 22 patients (44.0%), severe skin reaction only in 1 patient. Regarding acute postoperative morbidity, abscess and fistula formation was noted in 8 patients (16.0%), with anastomosis leakage in 7 (14%).
  
  
  CONCLUSIONS
  Preoperative radiotherapy appears to be a feasible therapeutic approach with moderate toxicity and the potential to induce down-staging. The data presented in this study confirm the preliminary reports on this neoadjuvant treatment.
authors.affiliation: Klinik und Poliklinik für Strahlentherapie und Radioonkologie der Universität München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schaffer
authors.forename: M
authors.initials: M
authors.lastname: Thoma
authors.forename: R
authors.initials: R
authors.lastname: Wilkowski
authors.forename: P
authors.initials: P
authors.lastname: Schaffer
authors.forename: E
authors.initials: E
authors.lastname: Dühmke
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality; D020266:Radiotherapy, Conformal; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil