title: Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone.
abstract: BACKGROUND
  Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB.
  
  
  METHODS
  Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection.
  
  
  RESULTS
  Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery (n = 106; 48 %) or had a less morbid procedure (n = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4-28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % (n = 24/25) for patients with planned joint/prosthesis replacement and 86 % (n = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5-17.9] months), local recurrence occurred in 17 (15 %) patients.
  
  
  CONCLUSIONS
  For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.
authors.affiliation: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Center and Institute of Oncology, Roentgen Str 5, 02-781, Warsaw, Poland, rutkowskip@coi.waw.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Grimer
authors.forename: Paul D
authors.initials: PD
authors.lastname: Stalley
authors.forename: Sander P D
authors.initials: SP
authors.lastname: Dijkstra
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pienkowski
authors.forename: Gualter
authors.initials: G
authors.lastname: Vaz
authors.forename: Jay S
authors.initials: JS
authors.lastname: Wunder
authors.forename: Leanne L
authors.initials: LL
authors.lastname: Seeger
authors.forename: Amy
authors.initials: A
authors.lastname: Feng
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Roberts
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bach
mesh_terms: D000328:Adult; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D000069448:Denosumab / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab