title: The use of vismodegib to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome.
abstract: OBJECTIVE
  Keratocystic odontogenic tumors (KCOTs) of the jaw affect more than 65% of patients with basal cell nevus syndrome (BCNS). Surgery frequently causes facial disfigurement and is not always curative. Most BCNS-related and some sporadic KCOTs have malignant activation of the Hedgehog signaling pathway.
  
  
  METHODS
  We examined the effect of vismodegib (an oral Hedgehog pathway inhibitor) on KCOT size in patients with BCNS enrolled in a clinical trial testing vismodegib for basal cell carcinoma prevention (NCT00957229), using pretreatment and posttreatment magnetic resonance imaging. Four men and 2 women had pretreatment KCOTs (mean longest diameter, 2.0 cm; range, 0.7-3.3 cm), occurring primarily in the mandible. Patients were treated with vismodegib, 150 mg/d, for a mean (SD) of 18.0 (4.8) months (range, 11-24 months). Four patients experienced a size reduction and 2 had no change. Vismodegib reduced the mean longest diameter of KCOTs in all patients by 1.0 cm (95% CI, 0.03-1.94; P = .02) or 50% from baseline. We observed no enlargement of existing KCOTs or new KCOT development.
  
  
  CONCLUSIONS
  Vismodegib shrinks some KCOTs in patients with BCNS and may offer an alternative to surgical therapy. These effects were maintained for at least 9 months after drug cessation in 1 patient. Further studies assessing long-term efficacy and optimal maintenance regimens should be performed.
authors.affiliation: Department of Dermatology, Stanford University, Redwood City, California.
authors.forename: Mina S
authors.initials: MS
authors.lastname: Ally
authors.affiliation: Department of Dermatology, Stanford University, Redwood City, California.
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Tang
authors.affiliation: Department of Radiology, Stanford University, Redwood City, California.
authors.forename: Timmy
authors.initials: T
authors.lastname: Joseph
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Department of Dermatology, Columbia University Medical Center, New York, New York.
authors.forename: Bobbye
authors.initials: B
authors.lastname: Thompson
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Joselyn
authors.initials: J
authors.lastname: Lindgren
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Maria Acosta
authors.initials: MA
authors.lastname: Raphael
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Department of Dermatology, Columbia University Medical Center, New York, New York.
authors.forename: Grace
authors.initials: G
authors.lastname: Ulerio
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Chanana
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Department of Dermatology, Columbia University Medical Center, New York, New York.
authors.forename: Julian M
authors.initials: JM
authors.lastname: Mackay-Wiggan
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Department of Dermatology, Columbia University Medical Center, New York, New York.
authors.forename: David R
authors.initials: DR
authors.lastname: Bickers
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Ervin H
authors.initials: EH
authors.lastname: Epstein
mesh_terms: D000328:Adult; D000813:Anilides / Q000008:administration & dosage*; D001478:Basal Cell Nevus Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009808:Odontogenic Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018579:Patient Selection; D011379:Prognosis; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000813:Anilides; C538724:HhAntag691; D011725:Pyridines