title: Activity of Sorafenib against desmoid tumor/deep fibromatosis.
abstract: BACKGROUND
  Desmoid tumors (deep fibromatoses) are clonal connective tissue malignancies that do not metastasize, but have a significant risk of local recurrence, and are associated with morbidity and occasionally mortality. Responses of desmoid patients to sorafenib on an expanded access program led us to review our experience.
  
  
  METHODS
  After Institutional Review Board (IRB) approval, we reviewed data for 26 patients with desmoid tumors treated with sorafenib. Sorafenib was administered at 400 mg oral daily and adjusted for toxicity.
  
  
  RESULTS
  Sorafenib was the first-line therapy in 11/26 patients and the remaining 15/26 had received a median of 2 prior lines of therapy. Twenty-three of 26 patients had shown evidence of progressive disease by imaging, whereas 3 patients had achieved maximum benefit or toxicity with chemotherapy. Sixteen of 22 (∼70%) patients reported significant improvement of symptoms. At a median of 6 months (2-29) of treatment, the best response evaluation criteria in solid tumors (RECIST) 1.1 response included 6/24 (25%) patients with partial response (PR), 17/24 (70%) with stable disease, and 1 with progression and death. Twelve of 13 (92%) patients evaluated by MRI had > 30% decrease in T2 signal intensity, an indirect metric for increased fibrosis and loss of cellularity. Eighty percent of patients with radiological benefit had extra-abdominal desmoids.
  
  
  CONCLUSIONS
  Sorafenib is active against desmoid tumors. A prospective, randomized clinical trial of sorafenib against other active agents is warranted. Loss of MRI T2 signal may be a useful surrogate for defining responses, but requires validation by examination of tumor pathology.
authors: Departments of Medicine, Radiology, Pathology, and Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors: Mrinal M
authors: MM
authors: Gounder
authors: Robert A
authors: RA
authors: Lefkowitz
authors: Mary Louise
authors: ML
authors: Keohan
authors: David R
authors: DR
authors: D'Adamo
authors: Meera
authors: M
authors: Hameed
authors: Cristina R
authors: CR
authors: Antonescu
authors: Samuel
authors: S
authors: Singer
authors: Katherine
authors: K
authors: Stout
authors: Linda
authors: L
authors: Ahn
authors: Robert G
authors: RG
authors: Maki
mesh_terms: D000293:Adolescent; D000328:Adult; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D018222:Desmoid Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome; D057832:Watchful Waiting; D055815:Young Adult
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib