title: Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation.
abstract: OBJECTIVE
  To assess the potential downstaging of advanced rectal cancer with combined preoperative chemoradiation.
  
  
  METHODS
  Thirty-one patients with fixed rectal cancers (stage > or = cT3) were treated with concomitant preoperative chemotherapy and high-dose radiation in an effort to improve resectability. Three (10%) patients had partially fixed low rectal cancers, 24 (77%) patients had fixed tumors, and 4 (13%) had advanced fixation with pelvic sidewall invasion. Radiation was delivered to the whole pelvis using shaped anterior and posterior and lateral fields to 45 Gy followed by a boost to the tumor. Median total radiation dose was 55.8 Gy. Chemotherapy consisted of low dose continuous infusion of 5-FU (200-300 mg/m2/day) for the duration of radiation treatment. All 31 patients underwent surgical resection of tumor 6-8 weeks following treatment. Median follow up is 24 months (range 9-60).
  
  
  RESULTS
  Twenty-three (74%) of the tumors were clinically downstaged following preoperative treatment. Of 24 fixed cancers, 11 (46%) became mobile, 6 (25%) became partially fixed, and 7 remained fixed. Of the four tumors with advanced fixation, two (50%) became mobile and two (50%) no longer had tumor extension to the pelvic sidewall. Two of the three initially partially fixed cancers became mobile and one remained partially fixed. Following surgery, the pathologic postradiation T-stages were as follows: T0: 10%, T1: 0%, T2: 32%, T3: 42%, and T4:16%. Seven patients (23%) were also node-positive (T0-2: 2, T3: 4, T4: 1), and two patients (6%) had liver metastases at surgery. Preoperative chemoradiation was well tolerated. There was no significant hematological toxicity. Acute grade 3 gastrointestinal toxicity was seen in six patients requiring a short hospitalization for dehydration and/or abdominal discomfort. No patient developed grade 4 toxicity. Five patients (16%) developed local recurrence of disease (T0-2: 0/13, T3: 1/13, and T4: 4/5). The actuarial 3-year survival is 68%.
  
  
  CONCLUSIONS
  Concomitant preoperative chemoradiation using low dose continuous infusional 5-FU for advanced rectal cancer is relatively safe with acceptable morbidity. This approach is associated with considerable clinical and pathologic downstaging of cancer. Tumor resectability is improved with potential for improved local control of disease and survival.
authors.affiliation: Department of Radiation Oncology and Nuclear Medicine, Thomas Jefferson University Hospital, Philadelphia, PA.
authors.forename: E T
authors.initials: ET
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: H
authors.initials: H
authors.lastname: Brodovsky
authors.forename: G
authors.initials: G
authors.lastname: Fishbein
authors.forename: G
authors.initials: G
authors.lastname: Marks
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011878:Radiotherapy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
chemical_list: D005472:Fluorouracil