title: 124I PET/CT to Predict the Outcome of Blind 131I Treatment in Patients with Biochemical Recurrence of Differentiated Thyroid Cancer: Results of a Multicenter Diagnostic Cohort Study (THYROPET).
abstract: Patients with suspected recurrence from differentiated thyroid carcinoma, based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Because standard imaging has a low yield identifying potential recurrence, blind (131)I treatment is often applied. However, a tumor-negative (131)I whole-body scintigraphy (WBS) prevails in 38%-50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that (124)I PET/CT can identify the patients with a tumor-negative posttherapy (131)I WBS.
  
  
  METHODS
  Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind (131)I therapy. All patients underwent (124)I PET/CT after administration of recombinant human thyroid-stimulating hormone. Subsequently, after 4-6 wk of thyroid hormone withdrawal patients were treated with 5.5-7.4 GBq of (131)I, followed by WBS a week later. The primary endpoint was the number of (131)I therapies that could have been omitted using the predicted outcome of the (124)I PET/CT, operationalized as the concordance of tumor detection by (124)I PET/CT, using post-(131)I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative (124)I PET/CT and a positive posttherapy (131)I scan.
  
  
  RESULTS
  After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at (131)I therapy was 28 μg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative (124)I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive (124)I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of (124)I PET/CT were 44% (confidence interval [CI], 14%-79%), 100% (CI, 63%-100%), 62% (CI, 32%-86%), and 100% (CI, 40%-100%), respectively. Implementation of (124)I PET in this setting would have led to 47% (8/17) less futile (131)I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy.
  
  
  CONCLUSIONS
  In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of (124)I PET/CT after recombinant human thyroid-stimulating hormone (124)I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind (131)I therapy.
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands j.kist@nki.nl.
authors.forename: Jakob W
authors.initials: JW
authors.lastname: Kist
authors.affiliation: Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Keizer
authors.affiliation: Department of Diagnostics, Groene Hart Ziekenhuis, Gouda, The Netherlands.
authors.forename: Manfred
authors.initials: M
authors.lastname: van der Vlies
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Brouwers
authors.affiliation: Department of Nuclear Medicine, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
authors.forename: Dyde A
authors.initials: DA
authors.lastname: Huysmans
authors.affiliation: Department of Nuclear Medicine, Medical Center Alkmaar, Alkmaar, The Netherlands.
authors.forename: Friso M
authors.initials: FM
authors.lastname: van der Zant
authors.affiliation: Department of Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands; and.
authors.forename: Rick
authors.initials: R
authors.lastname: Hermsen
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Marcel P M
authors.initials: MP
authors.lastname: Stokkel
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.forename: Wouter V
authors.initials: WV
authors.lastname: Vogel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D012008:Recurrence; D013954:Thyroglobulin / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes; D013954:Thyroglobulin
keywords: 124I PET/CT; 131I; differentiated thyroid cancer; radioactive iodine