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)

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 ¹³¹I treatment is often applied. However, a tumor-negative ¹³¹I whole-body scintigraphy (WBS) prevails in 38% 50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that ¹²⁴I PET/CT can identify the patients with a tumor-negative posttherapy ¹³¹I WBS. Methods: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind ¹³¹I therapy. All patients underwent ¹²⁴I PET/CT after administration of recombinant human thyroidstimulating hormone. Subsequently, after 4 6 wk of thyroid hormone withdrawal patients were treated with 5.5 7.4 GBq of ¹³¹I, followed by WBS a week later. The primary endpoint was the number of ¹³¹I therapies that could have been omitted using the predicted outcome of the ¹²⁴I PET/CT, operationalized as the concordance of tumor detection by ¹²⁴I PET/CT, using post-¹³¹I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative ¹²⁴I PET/CT and a positive posttherapy ¹³¹I scan. Results: After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at ¹³¹I therapy was 28 μg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative ¹²⁴I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive ¹²⁴I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of ¹²⁴I 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 ¹²⁴I PET in this setting would have led to 47% (8/17) less futile ¹³¹I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy. Conclusion: In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of ¹²⁴I PET/CT after recombinant human thyroidstimulating hormone ¹²⁴I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind ¹³¹I therapy. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.