title: Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis.
abstract: OBJECTIVE
  Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease.
  
  
  METHODS
  We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors.
  
  
  RESULTS
  WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of café-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10).
  
  
  CONCLUSIONS
  WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations.
authors.affiliation: Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, United States of America. splotkin@partners.org
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Bredella
authors.forename: Wenli
authors.initials: W
authors.lastname: Cai
authors.forename: Ara
authors.initials: A
authors.lastname: Kassarjian
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Harris
authors.forename: Sonia
authors.initials: S
authors.lastname: Esparza
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Merker
authors.forename: Lance L
authors.initials: LL
authors.lastname: Munn
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Manor
authors.initials: M
authors.lastname: Askenazi
authors.forename: Rosa
authors.initials: R
authors.lastname: Nguyen
authors.forename: Ralph
authors.initials: R
authors.lastname: Wenzel
authors.forename: Victor F
authors.initials: VF
authors.lastname: Mautner
mesh_terms: D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000175:diagnosis / Q000473:pathology*; D017253:Neurofibromatoses / Q000175:diagnosis / Q000473:pathology*; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000473:pathology*; D016518:Neurofibromatosis 2 / Q000175:diagnosis / Q000473:pathology*; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D012878:Skin Neoplasms / Q000175:diagnosis / Q000473:pathology*; D047368:Tumor Burden; D051598:Whole Body Imaging