title: Patient-reported Symptoms of Tenosynovial Giant Cell Tumors.
abstract: Tenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor-bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition.
  
  
  
  PRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively.
  
  
  
  Of the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27-56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n = 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGCT, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time.
  
  
  
  This study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369).
authors.affiliation: Evidera, Bethesda, Maryland. Electronic address: heather.gelhorn@evidera.com.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Gelhorn
authors.affiliation: Plexxikon Inc, Berkeley, California.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tong
authors.affiliation: Evidera, Bethesda, Maryland.
authors.forename: Kelly
authors.initials: K
authors.lastname: McQuarrie
authors.affiliation: Evidera, Bethesda, Maryland.
authors.forename: Christina
authors.initials: C
authors.lastname: Vernon
authors.affiliation: Evidera, Bethesda, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hanlon
authors.affiliation: Daiichi Sankyo Development Ltd, Buckinghamshire, United Kingdom.
authors.forename: Grant
authors.initials: G
authors.lastname: Maclaine
authors.affiliation: Evidera, Bethesda, Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Lenderking
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, New Jersey.
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.affiliation: Evidera, Bethesda, Maryland.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Speck
authors.affiliation: Cooper University Health Center, Orthopaedic Oncology Center, Camden, New Jersey.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lackman
authors.affiliation: Ronal Reagan UCLA Medical Center, Los Angeles, California.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Bukata
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
authors.forename: John H
authors.initials: JH
authors.lastname: Healey
authors.affiliation: Vanderbilt University Medical Center, Hematology/Oncology, Nashville, Tennessee.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Keedy
authors.affiliation: Texas Oncology-Tyler, Tyler, TX.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Anthony
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wagner
authors.affiliation: HonorHealth & Translational Genomics Research Institute, Scottsdale, Arizona.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.affiliation: Ronal Reagan UCLA Medical Center, Los Angeles, California.
authors.forename: Arun S
authors.initials: AS
authors.lastname: Singh
authors.affiliation: Sammons Cancer Center/US Oncology, Dallas, Texas.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Becerra
authors.affiliation: Plexxikon Inc, Berkeley, California.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Plexxikon Inc, Berkeley, California.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Lin
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
authors.forename: William D
authors.initials: WD
authors.lastname: Tap
mesh_terms: D000328:Adult; D005260:Female; D000070779:Giant Cell Tumor of Tendon Sheath; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D016896:Treatment Outcome
keywords: PROMIS; giant cell tumors of the tendon sheath (GCT-TS); patient-reported outcomes (PRO); pigmented villonodular synovitis (PVNS); tenosynovial giant cell tumor (TGCT)