title: Intensity modulated radiation therapy reduces gastrointestinal toxicity in locally advanced pancreas cancer.
abstract: OBJECTIVE
  We compared gastrointestinal (GI) and hematologic toxicity in patients with locally advanced pancreas cancer (LAPC) undergoing definitive chemoradiation using intensity modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT) planning.
  
  
  METHODS
  We retrospectively studied 205 patients with LAPC undergoing IMRT (n = 134) and 3D-CRT (n = 71) between May 2003 and March 2012. Patient, tumor, and treatment characteristics and acute GI/hematology toxicity according to the Common Terminology Criteria for Adverse Events, version 3.0, were recorded. Multivariable logistic regression models were used to test association between acute grade 2+ GI and hematologic toxicity outcomes and predictors. Propensity score analysis for grade 2+ GI toxicity was performed to reduce bias for confounding variables: age, gender, radiation dose, field size, and chemotherapy type.
  
  
  RESULTS
  Median follow-up time for survivors was 22 months and was similar between groups. Median RT dose was significantly higher for IMRT versus 3D-CRT (5600 cGy vs 5040 cGy, P < .001); concurrent chemotherapy was mainly gemcitabine (56%) or 5-fluorouracil (38%). Grade 2+ GI toxicity occurred in 34% (n = 24) of 3D-CRT compared with 16% (n = 21) of IMRT patients. Using propensity score analysis, 3D-CRT had significantly higher grade 2+ GI toxicity (odds ratio, 1.26; 95% confidence interval, 1.08-1.45; P = .001). Grade 2+ hematologic toxicity was similar between IMRT and 3D-CRT groups, but was significantly greater in recipients of concurrent gemcitabine than in 5-fluorouracil (62% vs 29%, P < .0001).
  
  
  CONCLUSIONS
  IMRT is associated with significant lower grade 2+ GI toxicity versus 3D-CRT for patients undergoing definitive chemoradiation therapy for LAPC. Because IMRT is better tolerated at higher doses and may allow further dose escalation, potentially improving local control for this aggressive disease. Further prospective studies of dose-escalated chemoradiation using IMRT are warranted.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Shreya
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Lajhem
authors.initials: L
authors.lastname: Cambridge
authors.affiliation: Department of Radiation Oncology, Tenon Hospital, APHP, University Paris VI, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Huguet
authors.affiliation: Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Chou
authors.affiliation: Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wu
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: karyn.goodman@ucdenver.edu.
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
mesh_terms: D059248:Chemoradiotherapy; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011880:Radiotherapy Planning, Computer-Assisted / Q000009:adverse effects / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies