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 thyroidstimulating 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. Conclusion: 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 thyroidstimulating hormone 124 I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind 131 I therapy.

Utility of I‐124 PET/CT in identifying radioiodine avid lesions in differentiated thyroid cancer: a systematic review and meta‐analysis

“…Eight studies were initially identified in the systematic review as potentially qualified for inclusion in the meta‐analysis . On further assessment, three of these studies were excluded .…”

THYROPET Study: Is It Biology or Technology That Is the Issue?

“…REPLY: Thank you for the opportunity to respond to the letter to the editor by Pattison et al regarding our article presenting the results of the THYROPET study (1). That study showed that after preparation with recombinant human thyroid-stimulating hormone (rh-TSH), 124 I PET/CT could not predict the outcome of the posttherapy 131 I scan after thyroid hormone withdrawal (THW) in patients with suspected recurrence of differentiated thyroid cancer.…”

“…We read with interest the results of the recently published THYROPET study (1), a prospective multicenter diagnostic cohort study testing the hypothesis that a recombinant human thyroid-stimulating hormone (rh-TSH)-stimulated 124 I PET/ CT scan can identify patients with a negative thyroxine withdrawal (T4WD) posttherapy 131 I scan and avoid futile treatment in patients with suspected recurrence of differentiated thyroid carcinoma. The trial was terminated prematurely because of a high number of falsenegative rh-TSH-stimulated 124 I PET/CT scans, which would preclude potential therapeutic benefit from 131 I therapy.…”

The role of iodine-124 positron emission tomography in molecular imaging

“…All lesions were accurately identified and the threshold absorbed dose value calculated for remnants and metastases to predict the achievement of complete response was calculated to be 90 Gy and 40 Gy respectively. In contrast, a multicenter diagnostic cohort study (THYROPET) by Kist et al [36], showed a high false negative rate of 124 I PET/CT in patients with biochemical evidence of recurrent thyroid cancer and negative ultrasound. However, the number of patients included in the study were small (n = 17) as it was terminated preliminarily, after three patients had a negative 124 I PET/CT and a positive post therapy 131 I.…”