SUN-385 - Oncocytic Thyroid Cancer Is Characterized by the Highest 68Ga-DOTATATE Uptake Amongst Metastatic Progressive Thyroid Cancers

Background
Peptide Receptor Radionuclide Therapy (PRRT) targeting somatostatin receptors type 2 (SSTR2) has improved the outcomes of patients with metastatic neuroendocrine tumors (NETs). Functional imaging with 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is used for SSTR2 quantification in NETs, with a Krenning score of ≥2 (tumor uptake ≥physiologic liver uptake) considered appropriate for PRRT. Moreover, an SUVmax of >15 is associated with improved objective response rate and longer progression free survival in patients with NETs. In contrast, evidence supporting the therapeutic relevance of SSTR2 targeting in treatment-refractory thyroid cancer (TC) remains limited and inconsistent. This study aimed to quantify and compare ⁶⁸Ga-DOTATATE uptake in metastatic medullary TC (MTC, neuroendocrine origin) with metastatic, radioiodine (RAI)-refractory epithelial-origin TCs: non-oncocytic differentiated TC (DTC) and oncocytic TC (OTC).

Material and Methods
We performed a prospective cohort study (ClinicalTrials.gov Identifier: NCT04927416) including adults with metastatic, progressive MTC, and RAI-refractory DTC and OTC. Power calculations for detecting a difference of uptake among the groups yielded a sample size of 54 participants. Recruitment has been completed for MTC and DTC groups, while the OTC cohort continues to recruit. Each patient underwent 68Ga-DOTATATE PET/CT as well as structural imaging. SUV quantification and Krenning scoring were independently performed by the two radiologists (NB, CM).

Results
The study included 49 patients: 18 with MTC, 18 with DTC and 13 with OTC (mean age: 44 ± 17 years, 28/49 (57%) male). A total of 441 metastatic lesions were analyzed, including 227 lymph nodes, 192 pulmonary nodules, 13 osseous lesions, and 9 other sites (pleural and thyroid bed). There was a significant difference in 68Ga-DOTATATE uptake across histologic groups (p < 0.001). Uptake was detected in 79/116 (68.1%) MTC lesions, 88/176 (50%) DTC lesions, and 110/149 (73.8%) OTC lesions. OTC lesions demonstrated the highest SUVmax, with a median of 8.5 [1-60] compared with MTC (4.5 [0.7-43], p< 0.001) and DTC (6.2 [1.1-27.2], p = 0.03). Among lesions demonstrating uptake, OTC had the highest proportion with Krenning score ≥2 (53/104 [51%]), versus MTC 24/104 (23.1%) and PTC 27/104 (26%), (p = 0.01). Moreover, the proportion of patients with SUVmax >15 in at least one metastatic lesion was significantly higher in OTC patients 9/13 (69.2%) compared with MTC 6/18 (33.3%) and DTC 3/18 (16.7%) patients (p = 0.01).
Conclusion
Among patients with metastatic, progressive TC, patients with OTC are characterized by the highest 68Ga-DOTATATE uptake. This data suggests that PRRT may represent a promising therapeutic option for patients with OTC, a population for whom effective treatment strategies remain limited.

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