title: Combined-modality therapy in locally advanced primary rectal cancer.
abstract: OBJECTIVE
  Patients with unresectable, locally advanced rectal cancer are reported to have a dismal prognosis. The aim of this study was to analyze the effect of combined-modality therapy on clinical outcome.
  
  
  METHODS
  From March 1990 to December 1997, 43 patients (28 males; median age, 62 years; median follow-up, 74 months) with locally advanced (T4 and/or N3) nonmetastatic rectal cancer received external-beam radiation (23.6 plus 23.6 Gy (split course), 8 patients; 45 Gy, 35 patients) plus 5-fluorouracil (96-hour continuous infusion, Days 1-4, at 1,000 mg/m(2)/day) and mitomycin C (10 mg/m, intravenous bolus, Day 1). Concomitant chemotherapy was repeated at the beginning of the second course (split-course group) or in the last week of radiotherapy (continuous-course group). After 6 to 8 weeks, patients were evaluated for surgical resection and intraoperative radiation therapy (10 to 15 Gy). Thereafter, adjuvant chemotherapy (5-fluorouracil plus leucovorin, 6-9 courses) was prescribed.
  
  
  RESULTS
  During chemoradiation, 5 patients (11.6 percent) developed Grade 3 to 4 hematologic toxicity. After chemoradiation, 29 patients (67.4 percent) had an objective clinical response (complete response, 2.3 percent; partial response, 65.1 percent). Thirty-eight patients underwent radical surgery (anterior resection, 24 patients; abdominoperineal resection, 14 patients; intraoperative radiation therapy boost on the tumor bed, 19 patients), and 2 patients had partial tumor resection. No perioperative deaths occurred in the patient group. Five-year survival and local control rates were 59.9 and 69.1 percent, respectively. Distant metastasis occurred in 44.2 percent of patients. Statistically significant relationships between intraoperative radiation therapy and local control (P = 0.0104), radical surgery and survival (P = 0.0120), and adjuvant chemotherapy and disease-free survival (P = 0.0112) were observed.
  
  
  CONCLUSIONS
  Our data suggest that combined-modality therapy was relatively well tolerated and resulted in good local control and survival. With regard to the impact of surgical resection on survival, additional studies aimed at improving the local response rate are necessary, whereas the positive impact of intraoperative radiotherapy on local control appears to justify the inclusion of this therapeutic modality in prospective multi-institutional trials.
authors.affiliation: Department of Surgical Sciences, Catholic University, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ratto
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
authors.forename: Brunella
authors.initials: B
authors.lastname: Barbaro
authors.forename: Claudio
authors.initials: C
authors.lastname: Coco
authors.forename: Luigi
authors.initials: L
authors.lastname: Sofo
authors.forename: Mario
authors.initials: M
authors.lastname: Balducci
authors.forename: Pier C
authors.initials: PC
authors.lastname: Gentile
authors.forename: Fabio
authors.initials: F
authors.lastname: Pacelli
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Doglietto
authors.forename: Aurelio
authors.initials: A
authors.lastname: Picciocchi
authors.forename: Numa
authors.initials: N
authors.lastname: Cellini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016685:Mitomycin; D005472:Fluorouracil