title: Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure.
abstract: OBJECTIVE
  To investigate treatment outcome and patterns of failure of sequential chemotherapy (CHT) and/or concurrent hypofractionated radiotherapy (RT) and CHT followed by surgery in locally advanced non-metastatic pancreatic adenocarcinoma.
  
  
  METHODS
  Seven patients with locally advanced but marginal resectable tumors (close contact but no signs of infiltration of the mesenteric vessels and/or vena portae) were treated with hypofractionated RT (5x3 Gy per week) and concurrent continuous infusion (300 mg/sqm/24 h, 7 days per week) of 5-fluorouracil (FU). Ten patients with locally advanced disease with radiologically suspected infiltration of the mesenteric vessels and/or v. portae were treated with 2 cycles of Cisplatin (75 mg/sqm) and Gemcitabine (2x1250 mg/sqm), and patients without tumor progression received the same concurrent RT/CHT as group 1. Four weeks after RT/CHT radical pancreatectomy was planned for patients with stable disease or remission.
  
  
  RESULTS
  Toxicity was low in both groups, with no CTC grade 4 toxicity. In group 1, RT/CHT was completed in all patients. There was no radiological remission, but stable disease in 5 out of 7 patients. All 5 patients underwent resection of the primary tumor with a R0-resection in 3 patients. In group 2, 8 patients completed CHT and RT/CHT treatment as planned. There were 3 with partial remission. Operation was done in 4 patients, but only one R0 resection was achieved. The median survival time for all 17 patients is 13 months, with 1- and 2-year survival being 53% and 18%, respectively. Local progression was observed in 9, peritoneal seeding in 7 and distant metastasis (mostly liver and lung) in 8 patients.
  
  
  CONCLUSIONS
  The neoadjuvant therapy could be administered with low toxicity. Results of this study warrant further investigation aiming at optimal tailoring in of this treatment approach in these two subgroups of patients.
authors.affiliation: Klinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universitaet Muenchen, Germany. frank.zimmermann@lrz.tu-muenchen.de
authors.forename: Frank B
authors.initials: FB
authors.lastname: Zimmermann
authors.forename: C
authors.initials: C
authors.lastname: Schuhmacher
authors.forename: C
authors.initials: C
authors.lastname: Lersch
authors.forename: B
authors.initials: B
authors.lastname: Bernhardt
authors.forename: P
authors.initials: P
authors.lastname: Pickel
authors.forename: J R
authors.initials: JR
authors.lastname: Siewert
authors.forename: M
authors.initials: M
authors.lastname: Molls
authors.forename: B
authors.initials: B
authors.lastname: Jeremic
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D016019:Survival Analysis; D017211:Treatment Failure