title: Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704--a phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas.
abstract: OBJECTIVE
  In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity.
  
  
  METHODS
  RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (<PP). Scoring occurred after therapy but before trial analysis and without knowledge of individual patient treatment outcomes. Scoring was done for all tumor locations and for the subset of pancreatic head location.
  
  
  RESULTS
  RT was scored for 416 patients: 216 PP and 200 <PP. For all pancreatic sites (head, body/tail) median survival (MS) for PP vs. <PP was 1.74 vs. 1.46 years (log-rank p = 0.0077). In multivariate analysis, PP vs. <PP score correlated more strongly with MS than assigned treatment arm (p = 0.014, p = NS, respectively); for patients with pancreatic head tumors, both PP score and gemcitabine treatment correlated with improved MS (p = 0.016, p = 0.043, respectively). For all tumor locations, PP score was associated with decreased risk of failure (p = 0.016) and, for gemcitabine patients, a trend toward reduced Grade 4/5 nonhematologic toxicity (p = 0.065).
  
  
  CONCLUSIONS
  This is the first Phase III, multicenter, adjuvant protocol for pancreatic adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.
authors.affiliation: Department of Radiation Oncology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Abrams
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Winter
authors.forename: William F
authors.initials: WF
authors.lastname: Regine
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.forename: John P
authors.initials: JP
authors.lastname: Hoffman
authors.forename: Robert
authors.initials: R
authors.lastname: Lustig
authors.forename: Andre A
authors.initials: AA
authors.lastname: Konski
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: Tyvin A
authors.initials: TA
authors.lastname: Rich
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D019983:Guideline Adherence; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine