Durski, Jolanta M.

Abstract INTRODUCTION Centiloid (CL) scaling standardizes amyloid positron emission tomography (PET) quantification across tracers and platforms; however, variability across software implementations may affect diagnostic classification. This study evaluated inter‐software variability and diagnostic performance across five platforms using identical 1 8 F‐florbetapir datasets. METHODS Retrospectively, 192 patients undergoing 1 8 F‐florbetapir PET/computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. CL values were generated using four US Food and Drug Administration (FDA) ‐cleared platforms and an in‐house Centiloid standard pipeline. Agreement was assessed using intraclass correlation coefficient, with bias and limits of agreement evaluated by linear modeling and Bland–Altman analysis. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and classification against visual interpretation. RESULTS Agreement was excellent (intraclass correlation coefficient [ICC] 0.969; 95%CI 0.961–0.975). Some platforms produced systematically higher CL values versus others slightly lower. LoA reached ± 30 CL. Diagnostic accuracy was high (area under the curve [AUC]: 0.949–0.975), with sensitivity 0.923–0.968 and specificity 0.667–0.806. DISCUSSION Despite excellent agreement, systematic differences persist and may affect classification near thresholds, supporting consistent use of a single processing pipeline.

Radioiodine ablation therapy is commonly used for patients with well-differentiated thyroid cancer. False-positive radioiodine uptake in benign cystic lesions on post-therapy SPECT/CT presents a recognized diagnostic challenge. Here, we present the case of a 33-year-old woman who underwent total thyroidectomy, followed by I-131 radioiodine therapy. Her post–I-131 therapy SPECT/CT revealed incidental radioiodine uptake in a diaphragmatic mesothelial cyst, prompting further investigation. She subsequently underwent a dedicated liver MRI and excision biopsy, both of which were negative for thyroid cancer metastasis. This case highlights the importance of identifying benign sources of radioiodine uptake to avoid unnecessary interventions.

Purpose: The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer. Material and methods: The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with “focal thyroid uptake” on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed. Results: Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included “focal thyroid uptake.” About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3). Conclusion: In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET.

Abstract Disclosure: S. Paknikar: None. D. Toro Tobon: None. J. Durski: None. H. Alkhateeb: None. M.M. Ryder: None. Introduction: Radioactive iodine (RAI) therapy-induced myelosuppression is a dose-limiting toxicity for RAI avid metastatic differentiated thyroid cancers. We describe a patient with exceptionally RAI avid metastatic follicular thyroid cancer (FTC) who underwent autologous stem cell cryopreservation (ASCC) to enable high dose I-131 treatments. Case: A 60-year-old woman with T1bN0M0 FTC underwent two-stage thyroidectomy and three doses of I-131 between 2002-2007 (434 mCi cumulative activity) due to incomplete biochemical response. She presented to our institution in 2015 with rising thyroglobulin (Tg) levels and lung nodules that were intensely RAI avid. She enrolled in a clinical trial of selumetinib versus placebo (for 1 month) followed by 150 mci I-131. She had a profound response with an 80% reduction in Tg and 50% tumor shrinkage. The following year her Tg rose to 8381 ng/mL and she developed biopsy proven, well differentiated metastatic FTC in the hip and liver. Lenvatinib treatment resulted in partial tumor and Tg response but was halted due to grade 3/4 toxicities. Tumor genomic interrogation revealed NRAS, PIK3CA, and TSH-R activating mutations, providing a causal explanation of her intensely RAI avid and responsive disease. Repeat I-131 therapy was facilitated by GM-CSF stimulated ASCC (8.57 x10(6) CD34+ cells/kg for two cycles) as a tool to help mitigate future potential RAI-induced myelosuppression. The patient received 295 mci I-131 followed by a 98% decrease in Tg and 20-25% shrinkage of liver metastases. Transient pancytopenia ensued but did not require autologous stem cell transplantation (ASCT). Due to insurance issues, the patient was lost to follow-up for two years. She returned with cachexia from severe, untreated thyrotoxicosis due to widespread functional, thyroxine producing metastatic disease. Anti-thyroid drug therapy (ATD) restored euthyroid status with significant clinical improvement. A non-stimulated I-123 whole body scan showed diffuse RAI avid disease with 88% whole body radioiodine retention at 48h. She received 125 mci I-131 with initial tumor response but with progression of bone marrow, calvaria, and retinal metastases. Six months later, a final dose of 253 mCi I-131 (cumulative activity 1,370 mCi) resulted in mixed tumor responses. Unfortunately, resection of a RAI refractory calvaria lesion postoperatively resulted in serious complications. ASCT and salvage treatments could not be pursued due to her impaired functional status. The patient pursued hospice care and passed away 20 years after her diagnosis. Conclusion: We characterize a patient with NRAS, PIK3CA and TSH-R mutant metastatic, thyroxine-producing FTC whose recurrences over 20 years retained intense RAI avidity and response to I-131 therapy. In cases with potential benefit from multiple high dose RAI therapies, ASCT may be a tool to mitigate I-131-induced myelosuppression. Presentation: 6/1/2024

Objective: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage 131 I therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients who underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT. Methods: This is a retrospective case series of 33 patients with response evaluation criteria in solid tumors (RECIST)-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic (Rochester, MN). All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone, or combination BRAF -MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high-dose 131 I therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTCs), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared with 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at 3 weeks on drug(s) alone. The redifferentiated subgroup, following high-dose 131 I therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy, and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer, 15.1% (5/33) died, and all had redifferentiated following RDT and received 131 I therapy. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following 131 I therapy in select patients with RAIR-DTC, particularly those with RAS -driven “follicular” phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.

Abstract A previously published model (Atkins) allows for calculation of 131I maximum tolerated activity on the basis of 48-hour whole-body retention of 131I on a pretherapy diagnostic scan. Our practice uses iodine 123I for diagnostic imaging of metastatic thyroid cancer for staging before 131I therapy, with images typically acquired 24 hours after administration of the radiopharmaceutical. We explored the feasibility of an additional 123I whole-body scan and retention measurement at 48 hours, with application of the model to estimate maximum tolerated activity of radioiodine before 131I treatment of metastatic thyroid cancer.