title: Changes in Liver Volume Observed Following Sorafenib and Liver Radiation Therapy.
abstract: OBJECTIVE
  The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT).
  
  
  METHODS
  Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT). Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs.
  
  
  RESULTS
  Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86).
  
  
  CONCLUSIONS
  Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaminath
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: James D
authors.initials: JD
authors.lastname: Brierley
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Rob
authors.initials: R
authors.lastname: Dinniwell
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kassam
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Coolens
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Kristy K
authors.initials: KK
authors.lastname: Brock
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. Electronic address: laura.dawson@rmp.uhn.on.ca.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D062485:Breath Holding; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011880:Radiotherapy Planning, Computer-Assisted; D061089:Radiotherapy, Image-Guided / Q000379:methods; D000077157:Sorafenib; D013997:Time Factors; D036542:Tomography, Spiral Computed; D047368:Tumor Burden / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib