title: Delaying chemoradiation until after completion of adjuvant chemotherapy for pancreatic cancer may not impact local control.
abstract: BACKGROUND
  Timing of administration of adjuvant chemoradiation (CRT) for pancreatic cancer has varied across studies. To date, the impact of timing of adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates the effect of timing of adjuvant CRT on locoregional control (LRC) and overall survival (OS).
  
  
  METHODS
  We performed a review of 159 patients with resected pancreatic adenocarcinoma who received adjuvant CRT between 1998 and 2010. Median dose of CRT was 50.4 Gy. The primary study variable was timing of CRT, dichotomized as immediate CRT versus delayed CRT. Consistent with Radiation Therapy Oncology Group (RTOG) 9704, immediate chemoradiation was defined as after ≤1 cycle of chemotherapy, whereas delayed CRT was defined as after >1 cycle. Cox multivariate analysis (MVA) was performed.
  
  
  RESULTS
  Median follow-up was 55 months. Seventy-four percent of patients received immediate CRT, and 26% patients received delayed CRT. Patients treated with delayed CRT were more likely to receive adjuvant gemcitabine (100% vs 53%; P < .001). Timing of adjuvant CRT was not associated with LRC or OS on univariate or MVA. Preoperative carcinoembryonic antigen ≥1.3 ng/mL (hazard ratio, 3.18; P = .017) and positive margins (hazard ratio, 5.35; P < .001) were associated with lower rates LRC on MVA. Higher lymph node positivity ratio and not receiving adjuvant gemcitabine were independently associated with worse OS.
  
  
  CONCLUSIONS
  Timing of adjuvant CRT for resectable pancreatic cancer may not significantly affect LRC or OS. These findings support the ongoing RTOG 0848 trial design, and provide reassurance that delaying CRT until completion of chemotherapy should not significantly impact LRC.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jwo@partners.org.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Wo
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Childs
authors.affiliation: Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Mamon
authors.affiliation: Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.affiliation: Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.affiliation: Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.affiliation: Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jill N
authors.initials: JN
authors.lastname: Allen
authors.affiliation: Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Wolpin
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chan
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Abrams
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: McCleary
authors.affiliation: Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Del Castillo
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
mesh_terms: D000704:Analysis of Variance; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D012189:Retrospective Studies