title: Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1.
abstract: OBJECTIVE
  Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN.
  
  
  METHODS
  The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials.
  
  
  RESULTS
  For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows.
  
  
  CONCLUSIONS
  These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs.
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK. splotkin@partners.org.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Davis
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Kent A
authors.initials: KA
authors.lastname: Robertson
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Srivandana
authors.initials: S
authors.lastname: Akshintala
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Allen
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisher
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Jaishri O
authors.initials: JO
authors.lastname: Blakeley
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Brigitte C
authors.initials: BC
authors.lastname: Widemann
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Rosalie E
authors.initials: RE
authors.lastname: Ferner
authors.affiliation: From the Neurology Department and Cancer Center (S.R.P.), Massachusetts General Hospital, Boston; Section of Pediatric Pulmonology, Allergy and Sleep Medicine (S.D.D.), and Stem Cell Transplantation Program (K.A.R.), Riley Children's Hospital, Indiana University School of Medicine, Indianapolis; Pediatric Oncology Branch (S.A., B.C.W.), National Cancer Institute, Bethesda, MD; Division of Pulmonary Medicine (J.A.), Division of Oncology (M.J.F.), and Sleep Center (C.L.M.), Children's Hospital of Philadelphia; Department of Pediatrics (M.J.F.) and Sleep Center (C.L.M.), The Perelman School of Medicine at the University of Pennsylvania (J.A.), Philadelphia; Department of Neurology (J.O.B.), John Hopkins Medical Institute, Baltimore, MD; and Department of Neurology (R.E.F.), Guy's and St. Thomas' NHS Foundation Trust and Institute of Psychiatry, King's College London, UK.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Marcus
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D008168:Lung / Q000503:physiopathology; D018318:Neurofibroma, Plexiform / Q000503:physiopathology / Q000628:therapy*; D009456:Neurofibromatosis 1 / Q000503:physiopathology / Q000628:therapy*; D009991:Oscillometry / Q000379:methods*; D017286:Polysomnography / Q000379:methods*; D012890:Sleep / Q000502:physiology; D013147:Spirometry / Q000379:methods*; D016896:Treatment Outcome