title: [18F]-Fluoromisonidazole positron emission tomography/computed tomography visualization of tumor hypoxia in patients with chordoma of the mobile and sacrococcygeal spine.
abstract: OBJECTIVE
  To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine.
  
  
  METHODS
  A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs.
  
  
  RESULTS
  The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm(3) vs 63.4 cm(3); P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs.
  
  
  CONCLUSIONS
  Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts. Electronic address: mcheney@lroc.harvard.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Cheney
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Diagnostic Radiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lim
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Winrich
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Anca L
authors.initials: AL
authors.lastname: Grosu
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Trofimov
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts; Centre of Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Depauw
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
authors.affiliation: Department of Orthopedic Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Schwab
authors.affiliation: Department of Orthopedic Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: DeLaney
mesh_terms: D000328:Adult; D000368:Aged; D015687:Cell Hypoxia; D002817:Chordoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D064847:Multimodal Imaging / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000378:metabolism*; D017785:Photons / Q000627:therapeutic use; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D061766:Proton Therapy; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012445:Sacrococcygeal Region / Q000000981:diagnostic imaging; D013125:Spinal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery; D014057:Tomography, X-Ray Computed / Q000379:methods; D047368:Tumor Burden
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole