title: A randomized controlled trial of lorazepam to reduce liver motion in patients receiving upper abdominal radiation therapy.
abstract: OBJECTIVE
  Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion.
  
  
  METHODS
  Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy.
  
  
  RESULTS
  Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant.
  
  
  CONCLUSIONS
  Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Tsang
authors.forename: Francine E M
authors.initials: FE
authors.lastname: Voncken
authors.forename: Regina V
authors.initials: RV
authors.lastname: Tse
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Rebecca K S
authors.initials: RK
authors.lastname: Wong
authors.forename: Rob E
authors.initials: RE
authors.lastname: Dinniwell
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: James D
authors.initials: JD
authors.lastname: Brierley
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Cummings
authors.forename: Anthony
authors.initials: A
authors.lastname: Brade
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054893:Cone-Beam Computed Tomography; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D008099:Liver / Q000000981:diagnostic imaging; D008140:Lorazepam / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects*; D015588:Observer Variation; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D012119:Respiration
chemical_list: D006993:Hypnotics and Sedatives; D008140:Lorazepam