title: Histopathological effects of preoperative chemoradiotherapy for pancreatic cancer: an analysis for the impact of radiation and gemcitabine doses.
abstract: OBJECTIVE
  Histopathological findings of patients who underwent resection for pancreatic adenocarcinoma (PC) after preoperative chemoradiotherapy (CRT) reportedly showed beneficial effects. The purpose of our study was to evaluate the correlation between histopathological effects (HE) of preoperative CRT and treatment parameters [radiation and gemcitabine (GEM) doses].
  
  
  METHODS
  HE of CRT were assessed on 158 primary lesions of 157 patients with PC who underwent pancreatic resection after preoperative CRT with GEM between January 2006 and December 2011. The radiation dose delivered to the primary tumor site and surrounding regional nodal areas was 50 Gy until September 2009 followed by the dose escalation of a 10 Gy boost added for delivery with the field-in-field technique to the roots of the celiac and superior mesenteric arteries. Intravenous administration of GEM (1000 /m(2)) was initiated concurrently on days 1, 8, and 15, every 4 weeks and generally repeated for 3 cycles. HE of CRT on the primary tumor were categorized based on the number of tumor cells destroyed.
  
  
  RESULTS
  The median overall survival time was 74.5 months and 3-year and 5-year survival rates were 64.3% and 54.5%, respectively. Dose-volume parameters of radiation such as D33 with a cut-off value of 51.6 Gy were correlated significantly with HE (p=.0230). Lesions having received GEM>7625 mg/m(2) before surgical resection more frequently showed positive HE (p=.0002). Multivariate logistic regression analysis demonstrated that both D33 and cumulative GEM dose were significant predictors of definite HE (p=.0110 and <.0001, respectively).
  
  
  CONCLUSIONS
  Our retrospective analysis showed that dose intensity of radiation and GEM is significantly related to HE of preoperative CRT for PC.
authors.affiliation: Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takero
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. Electronic address: teshima-te@mc.pref.osaka.jp.
authors.forename: Teruki
authors.initials: T
authors.lastname: Teshima
authors.affiliation: Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kinji
authors.initials: K
authors.lastname: Nishiyama
authors.affiliation: Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Konishi
authors.affiliation: Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohigashi
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D059248:Chemoradiotherapy / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D011829:Radiation Dosage; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Gemcitabine; Histopathological effects; Pancreatic cancer; Preoperative chemoradiotherapy