title: Intraoperative Radiotherapy in the Era of Intensive Neoadjuvant Chemotherapy and Chemoradiotherapy for Pancreatic Adenocarcinoma.
abstract: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic pancreatic adenocarcinoma (PDAC) have prompted incorporation of these regimens into neoadjuvant treatment of locally advanced unresectable PDAC. Whereas some patients remain unresectable on surgical exploration, others are able to undergo resection after intensive neoadjuvant treatment. We evaluated outcomes and toxicity associated with use of intensive neoadjuvant treatment followed by intraoperative radiotherapy (IORT) in combination with resection or exploratory laparotomy.
  
  
  
  We retrospectively analyzed patients with locally advanced unresectable or borderline-resectable PDAC who received intensive neoadjuvant treatment with induction chemotherapy and chemoradiotherapy followed by exploratory laparotomy in an IORT-equipped operating suite between 2010 and 2015. Surgical outcomes and overall survival (OS) were compared.
  
  
  
  Of 68 patients, 41 (60.3%) underwent resection, 18 (26.5%) had unresectable disease, and 9 (13.2%) had distant metastases. Of 41 resectable patients, 22 received IORT for close/positive resection margins on intraoperative frozen section. There was no significant difference in operative times or morbidity with addition of IORT to resection. Median OS was 26.6 months for all patients who underwent resection, 35.1 months for patients who underwent resection and IORT, and 24.5 months for patients who underwent resection alone (P=NS). Of 18 patients with unresectable disease, all but 1 received IORT, with median OS of 24.8 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative times or morbidity.
  
  
  
  IORT in addition to intensive neoadjuvant chemotherapy and chemoradiotherapy was not associated with increased toxicity when used with resection or exploratory laparotomy, and was associated with encouraging survival rates in patients with close/positive margins and patients with unresectable disease.
authors.affiliation: Harvard Radiation Oncology Program, Harvard Medical School.
authors.forename: Florence K
authors.initials: FK
authors.lastname: Keane
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Wo
authors.affiliation: Surgery.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.affiliation: Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.affiliation: Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.affiliation: Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA.
authors.forename: Jill N
authors.initials: JN
authors.lastname: Allen
authors.affiliation: Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA.
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.affiliation: Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA.
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: Surgery.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.affiliation: Surgery.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Del Castillo
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000401:mortality*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D007430:Intraoperative Care; D007813:Laparotomy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000401:mortality*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine