title: Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas.
abstract: OBJECTIVE
  The effects of preoperative versus postoperative fluorouracil (5-FU)-based chemotherapy and irradiation on treatment toxicity, duration of treatment, tumor recurrence, and survival were compared in patients who underwent potentially curative therapy for adenocarcinoma of the pancreatic head during a 5-year period.
  
  
  METHODS
  From July 1990 to July 1995, 142 patients with localized adenocarcinoma of the pancreatic head deemed resectable on the basis of radiographic images were treated with curative intent using a multimodality approach involving either preoperative or postoperative chemoradiation. Patients with biopsy confirmation of adenocarcinoma and a low-density mass in the pancreatic head identified by computed tomography (CT) received preoperative chemoradiation. Patients without a mass on CT or in whom the preoperative biopsy was negative underwent pancreaticoduodenectomy with planned postoperative chemoradiation. Protocol-based preoperative chemoradiation consisted of external-beam irradiation at a dose of 50.4 Gy (standard fractionation; 1.8 Gy/d, 5 d/wk) or 30 Gy (rapid fractionation; 3 Gy/d, 5 d/wk) combined with continuous infusion 5-FU (300 mg/m2/d, 5 d/wk). Postoperative chemoradiation combined 50.4 Gy of external-beam irradiation (standard fractionation) with continuous-infusion 5-FU.
  
  
  RESULTS
  No patient who received preoperative chemoradiation experienced a delay in surgery because of chemoradiation toxicity, but six of 25 eligible patients (24%) did not receive postoperative chemoradiation because of delayed recovery after pancreaticoduodenectomy. No significant differences in toxicities from chemoradiation were observed between groups. Patients treated with rapid-fractionation preoperative chemoradiation had a significantly (P < .01) shorter duration of treatment (median, 62.5 days) compared with patients who received postoperative chemoradiation (median, 98.5 days) or standard-fractionation preoperative chemoradiation (median, 91.0 days). At a median followup of 19 months, no significant differences in survival were observed between treatment groups. No patient who received preoperative chemoradiation and pancreaticoduodenectomy experienced a local recurrence; peritoneal (regional) recurrence occurred in 10% of these patients. Local or regional recurrence occurred in 21% of patients who received pancreaticoduodenectomy and postoperative chemoradiation.
  
  
  CONCLUSIONS
  Delivery of preoperative and postoperative chemoradiation in patients who underwent potentially curative pancreaticoduodenectomy for adenocarcinoma of the pancreatic head resulted in similar treatment toxicity, patterns of tumor recurrence, and survival. Rapid-fractionation preoperative chemoradiation ensured the delivery of all components of therapy to all eligible patients with a significantly shorter duration of treatment than with standard-fractionation chemoradiation given either before or after pancreaticoduodenectomy. Prolonged recovery after pancreaticoduodenectomy prevents the delivery of postoperative adjuvant chemoradiation in up to one fourth of eligible patients.
authors.affiliation: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Spitz
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.forename: P W
authors.initials: PW
authors.lastname: Pisters
authors.forename: A M
authors.initials: AM
authors.lastname: Lowy
authors.forename: C J
authors.initials: CJ
authors.lastname: Fenoglio
authors.forename: K R
authors.initials: KR
authors.lastname: Cleary
authors.forename: N A
authors.initials: NA
authors.lastname: Janjan
authors.forename: M S
authors.initials: MS
authors.lastname: Goswitz
authors.forename: T A
authors.initials: TA
authors.lastname: Rich
authors.forename: D B
authors.initials: DB
authors.lastname: Evans
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011446:Prospective Studies; D016019:Survival Analysis