title: Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer.
abstract: OBJECTIVE
  On the basis of the ACCORD trial, FOLFIRINOX is effective in metastatic pancreatic adenocarcinoma (PDAC), making it a rational choice for locally advanced PDAC (LA). Aims of this study are to evaluate the accuracy of imaging in determining the resectability of PDAC and to determine the surgical and clinicopathologic outcomes of pancreatic resections after neoadjuvant FOLFIRINOX therapy.
  
  
  METHODS
  Clinicopathologic data were retrospectively collected for surgical PDAC patients receiving neoadjuvant FOLFIRINOX or no neoadjuvant therapy between April 2011 and February 2014. Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract consensus guidelines defined LA and borderline. Imaging was reviewed by a blinded senior pancreatic surgeon.
  
  
  RESULTS
  Of 188 patients undergoing resection for PDAC, 40 LA/borderline received FOLFIRINOX and 87 received no neoadjuvant therapy. FOLFIRINOX resulted in a significant decrease in tumor size, yet 19 patients were still classified as LA and 9 as borderline. Despite post-FOLFIRINOX imaging suggesting continued unresectability, 92% had an R0 resection. When compared with no neoadjuvant therapy, FOLFIRINOX resulted in significantly longer operative times (393 vs 300 minutes) and blood loss (600 vs 400 mL), but significantly lower operative morbidity (36% vs 63%) and no postoperative pancreatic fistulas. Length of stay (6 vs 7 days), readmissions (20% vs 30%), and mortality were equivalent (1% vs 0%). On final pathology, the FOLFIRINOX group had a significant decrease in lymph node positivity (35% vs 79%) and perineural invasion (72% vs 95%). Median follow-up was 11 months with a significant increase in overall survival with FOLFIRINOX.
  
  
  CONCLUSIONS
  After neoadjuvant FOLFIRINOX imaging no longer predicts unresectability. Traditional pathologic predictors of survival are improved, and morbidity is decreased in comparison to patients with clearly resectable cancers at the time of presentation.
authors.affiliation: *Department of Surgery †Department of Radiation Oncology; and ‡Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marchegiani
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.forename: Erin I
authors.initials: EI
authors.lastname: McDonnell
authors.forename: Francesco
authors.initials: F
authors.lastname: Sabbatino
authors.forename: Daniela Dias
authors.initials: DD
authors.lastname: Santos
authors.forename: Jill N
authors.initials: JN
authors.lastname: Allen
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Jason E
authors.initials: JE
authors.lastname: Faris
authors.forename: Lipika
authors.initials: L
authors.lastname: Goyal
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.forename: Janet E
authors.initials: JE
authors.lastname: Murphy
authors.forename: David T
authors.initials: DT
authors.lastname: Ting
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Wo
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Warshaw
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-del Castillo
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D021621:Imaging, Three-Dimensional; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D012189:Retrospective Studies; D054894:Spiral Cone-Beam Computed Tomography; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin