title: Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective phase II trial.
abstract: OBJECTIVE
  To evaluate the morbidity of pancreaticoduodenectomy after neoadjuvant chemotherapy for resectable pancreatic cancer and to assess its histologic and metabolic response.
  
  
  BACKGROUND
  Adjuvant chemotherapy improves the outcome of pancreatic cancer, but 25% of patients remain unfit after surgery. Neoadjuvant chemotherapy can be offered to all patients in a multimodality approach, but its efficacy and surgical morbidity are unknown.
  
  
  METHODS
  Patients with resectable, cytologically proven adenocarcinoma of the pancreatic head received 4 bi-weekly cycles of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) in this prospective phase II trial. Staging and restaging included chest x-ray, abdominal computed tomography (CT), positron emission tomography (PET)/CT, endoscopic ultrasound, and laparoscopy. Fluorodeoxyglucose uptake was quantified by the standard-uptake value (SUV) on baseline and restaging PET/CT. Immunohistochemistry for GLUT-1 and Ki-67 was performed. The histologic response, cytopathic effects, and surgical complications were graded by respective scores.
  
  
  RESULTS
  Twenty-four of 28 patients had resection for histologically confirmed adenocarcinoma. The surgical morbidity was low without perioperative death and one pancreatic fistula. Histologic response was documented in 54% and cytopathic effects in 83% of the patients. A significant SUV decrease occurred during chemotherapy (P = 0.031), which correlated with the baseline SUV (P = 0.001), Ki-67 expression (P = 0.016), and histologic response (P = 0.01). Neither the metabolic nor the histologic response was predictive of the median disease-free (9.2 months) or overall survival (26.5 months).
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy induced a significant metabolic and histologic response, which was best predicted by PET. Most importantly, surgery after neoadjuvant chemotherapy for pancreatic cancer was safe.
authors.affiliation: Swiss HPB-Center, Department of Surgery and Institute of Surgical Pathology, Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Heinrich
authors.forename: Markus
authors.initials: M
authors.lastname: Schäfer
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Hany
authors.forename: Ujwal
authors.initials: U
authors.lastname: Bhure
authors.forename: Bernhard C
authors.initials: BC
authors.lastname: Pestalozzi
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018395:CA-19-9 Antigen / Q000097:blood; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D006801:Humans; D009017:Morbidity; D020360:Neoadjuvant Therapy; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016577:Pancreaticoduodenectomy; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D000093542:Gemcitabine
chemical_list: D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine