title: Neoadjuvant radiochemotherapy in the treatment of fixed and semi-fixed rectal tumors. Analysis of results and prognostic factors.
abstract: OBJECTIVE
  To report the retrospective analysis of patients with locally advanced rectal cancer treated with neodjuvant radiochemotherapy.
  
  
  METHODS
  From January 1994 to December 2003, 101 patients with fixed (25%) or semi-fixed (75%) rectal adenocarcinoma were treated by preoperative radiotherapy with a dose of 45 Gy at the whole pelvis and 50.4 Gy at primary tumor, concomitant to four weekly chemotherapies with 5-Fluorouracil (425 mg/m2) and Leucovorin (20 mg/m2). In 71 patients (70.3%) the primary tumor was located up to 6 cm from the anal verge and in 30 (29.7%) from 6.5 cm to 10 cm. Age, gender, tumor fixation, tumor distance from the anal verge, clinical response, surgical technique, and postoperative TNM stage were the prognostic factors analyzed for overall survival (OS), disease-free survival (DFS), and local control (LC) at five years.
  
  
  RESULTS
  Median follow-up time was 38 months (range, 2-141). Complete response was observed in eight patients (7.9%), partial in 54 (53.4%) and absence in 39 (38.7%). OS, DFS and LC were 52.6%, 53.8%, and 75.9%, respectively. Distant metastasis occurred in 40 (39.6%) patients, local recurrence in 20 (19.8%) and both in 16 (15.8%). Patients with fixed tumors had lower OS (17% Vs 65.6%; p < 0.001), DFS (31.2% Vs 60.9%; p = 0.005), and LC (58% Vs 82%; p = 0.004). Patients with tumors more than 6 cm above the anal verge had better LC (93% Vs 69%; p = 0.04). The postoperative TNM stage was a significant factor for DFS (I:64.1%, II:69.6%, III:35.2%, IV:11.1%; p < 0.001) and for LC (I:75.7%, II: 92.9%, III:54.1%, IV:100%; p = 0.005). Patients with positive lymph nodes had worse OS (37.9% Vs 70.4%, p = 0.006), DFS (32% Vs 72.7%, p < 0.001) and LC (56.2% Vs 93.4%; p < 0.001).
  
  
  CONCLUSIONS
  This study suggests that the neoadjuvant treatment employed was effective for local control. Fixation of the lesion and lymph nodes metastasis were the main adverse prognostic factors. Distant failures were frequent, supporting the need of new drugs for adjuvant chemotherapy.
authors.affiliation: Department of Radiation Oncology, Hospital do Câncer A, C, Camargo, Rua Prof, Antonio Prudente, 211, São Paulo, SP 01509-900, Brazil. rferrigno@uol.com.br
authors.forename: Robson
authors.initials: R
authors.lastname: Ferrigno
authors.forename: Paulo Eduardo Ribeiro dos Santos
authors.initials: PE
authors.lastname: Novaes
authors.forename: Maria Letícia Gobo
authors.initials: ML
authors.lastname: Silva
authors.forename: Ines Nobuko
authors.initials: IN
authors.lastname: Nishimoto
authors.forename: Wilson Toshihiko
authors.initials: WT
authors.lastname: Nakagawa
authors.forename: Benedito Mauro
authors.initials: BM
authors.lastname: Rossi
authors.forename: Fábio de Oliveira
authors.initials: Fde O
authors.lastname: Ferreira
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011878:Radiotherapy / Q000379:methods*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D012189:Retrospective Studies
chemical_list: D002955:Leucovorin; D005472:Fluorouracil