CLERAD-PROBE: Dosimetric analysis of I-124 PET–guided remnant radioiodine ablation in differentiated thyroid carcinoma.

Abstract

3068 Background: The role of adjuvant radioiodine therapy (RIT) in differentiated thyroid carcinoma (DTC) remains controversial due to a lack of long-term data from randomized controlled trials. Consequently, international guidelines diverge; while some advocate broad application, others prioritize a restrictive, risk-adapted approach. The CLERAD-PROBE trial aims to bridge this gap by comparing both strategies regarding blood dose — as an established surrogate for secondary malignancy risk — and oncological outcomes. Methods: CLERAD-PROBE is a prospective, randomized, bicentric study (NCT01704586) in adult DTC patients, excluding those with unifocal papillary microcarcinomas ≤ 10 mm limited to the thyroid. Following thyroidectomy, patients in Arm 1 underwent I-124 PET for staging and dosimetry. Adjuvant RIT was administered if one or multiple of the following risk factors were present: incomplete surgical resection, tumor size >4cm or extrathyroidal extent, lymph node metastases and age ≥ 45 years, distant metastases, and/or iodine-avid lesions on I-124 PET. In Arm 2, adjuvant RIT was generally performed. Follow-up was performed every 4–6 months using thyroglobulin measurements and cervical ultrasound. The primary endpoint was the mean blood dose after complete remission or 18 months. Secondary endpoints included progression- and recurrence-free survival at 3 and 10 years. Results: The primary endpoint was evaluable in 315 patients, enrolled from May 2015 to May 2021 (148 in Arm 1, 167 in Arm 2). Study arms were matched with regards to histology, age, and tumor/nodal stage, though Arm 1 had significantly fewer men (22% vs. 34%, p = 0.02). I-124 PET identified lymph node metastases in 49 patients and distant metastases in 13 patients. RIT was performed in 68 of 148 (46%) patients in Arm 1. Of these, 13 patients with low-risk carcinoma underwent RIT because of new metastases found on I-124 PET. The mean absorbed blood doses (252 mGy vs 447 mGy, range: 4 - 3217 mGy vs. 48 - 2520 mGy; p < 0.001) and administered I-131-activities (2.3 GBq vs. 4.9 GBq; range: 0 – 18.6 GBq vs. 1.0 – 26.2 GBq; p < 0.001) were lower in Arm 1. Conclusions: I-124 PET identifies persistent, iodine-avid disease in patients who would not routinely receive adjuvant RIT pursuant to ATA Guidelines, while enabling individualized selection in the others to minimize secondary malignancy risk. The impact on long term oncological outcomes has yet to be determined. Three years follow-up analyses evaluating recurrence rates and overall oncological safety are currently in progress and will be presented at the congress. Clinical trial information: NCT01704586 .