Ryder, Mabel

Abstract Context. Thyroid nodule ultrasound findings are crucial in guiding management decisions for patients with thyroid nodules. However, the frequency with which ultrasound images are discussed and reviewed with patients during clinical visits is not well understood. Objective. To assess how often thyroid ultrasound images are shown and discussed with patients during consultations, and to identify predictors of image review during clinical visits. Design and setting. Secondary analysis of a multicenter pilot randomized clinical trial conducted at two academic medical centers in the United States. Participants. Adults undergoing evaluation for thyroid nodules. Intervention. Participants were randomized to receive either usual care or care enhanced with a conversation aid. Main Outcome Measures. The primary outcome was the frequency of thyroid nodule imaging review evaluated as a binary outcome. Secondary outcomes included evaluation of predictors of image discussion. Results. Eighty-five patients were evaluated. Most participants were women (80%), mean age (60 years, SD 16), and White (86%), undergoing new patient visits (84%). Thyroid nodule ultrasound images were reviewed with patients in 53% of visits (45/85), and in all cases, clinicians initiated the imaging discussion. Predictors of image review included type of consultation (new patient visit) (OR 10.6, 95% CI: 1.79, 62.3). Age, sex, study arm, thyroid nodule size or cancer risk and plan of care (e.g., completing a biopsy) were not statistically associated with review of clinical images. Conclusions. Review of thyroid ultrasound images during clinical visits is relatively common, with consultation type serving as significant predictor.

Abstract Disclosure: S. Saad-Omer: None. M. Stan: None. M.R. Castro: None. J. Brito: None. J.E. Hallanger-Johnson: None. M.M. Ryder: None. Background: Thyroid fine needle aspiration (FNA) is a widely utilized diagnostic tool for evaluating thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) provides a standardized framework for classifying cytologic findings and guiding management. This study retrospectively reviews thyroid FNA cases at a large academic institution to analyze the distribution of Bethesda classifications.Methods: A retrospective review was conducted of all thyroid FNA cases done in the department of Endocrinology at a large academic institution performed from January 1st 2019 to October 3rd 2023. Thyroid FNA results were divided into categories according to the Bethesda classification system, such as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm (FN), suspicious for malignancy, malignancy and non-diagnostic. FNA results that were not able to be classified were labelled as other.Results: A total of 3,291 thyroid FNA cases were included in the analysis. The distribution of cases across the Bethesda categories revealed a significant proportion of benign findings, with 73.6% classified as benign. This was followed by 8.1% follicular neoplasm, 6.56% Papillary Thyroid Cancer, 6.62% Non-diagnostic, 2.4% Atypical, and 2.3% Suspicious. 0.5% of FNA results were classified as other.Conclusion: Overall our cohort was found to have similar findings in terms of benign and confirmed PTC nodules compared to recent literature; however, the rate of atypical and non-diagnostic nodules was found to be lower. Presentation: Monday, July 14, 2025

6008 Background: ATC patients present with advanced, often surgically unresectable disease with historically dismal prognosis. Median PFS and OS of DT without pembrolizumab were 6.7 and 13.5 months, respectively, in the ROAR trial. Neoadjuvant DTP achieved locoregional control without radical surgery in a retrospective series of BRAF m-ATC patients, providing rationale to evaluate efficacy and safety in a phase 2 prospective trial. Methods: In this single-arm multicenter phase 2 trial, patients with BRAF m-ATC stage IVB/IVC were enrolled in 5 US centers. Following a 3-6 week run-in with D (150 mg BID) and T (2 mg daily), P (200 mg Q3W) was added, with restaging every three (21-day) cycles. Post-operatively, patients continued P (or DTP) with radiotherapy or transitioned directly to adjuvant DTP (up to 26 cycles). Primary endpoints included R0/R1 resection rate (historically 5%) and overall survival (OS). Secondary endpoints included RECIST 1.1 response after DTP and progression-free survival (PFS). Results: Between 9/2021-1/2025, 42 patients were enrolled; 36 are included in the current analysis (3 not evaluable, 3 pending surgery) (Table). Patients received median 4 (range: 2-7) neoadjuvant DTP cycles, with 26 (72%) achieving radiographic PR/CR. 30 patients (83%) had surgery after neoadjuvant DTP, achieving R0/R1 resection in 29/30 (97%). Mean surgical morbidity score (0-4 scale, 4=unresectable) improved from 3.3 to 1.6 after DTP (p<0.01). Complete ATC pathologic response occurred in 20/30 patients (67%), while 10/30 (33%) had residual ATC in the surgical specimen. Postoperatively, 11/30 (37%) received adjuvant neck radiation, and 28/36 (78%) completed a median of 11 (range: 1-26) adjuvant DTP cycles. With median follow up 18 months, 15/36 (42%) patients died. Median OS was 20 months (95% CI: 12.6-NR); 1- and 2-year OS were 71% and 48%. Complete pathologic responders had better 2-year OS than those with residual ATC (69% vs. 22%, p=0.02). Median PFS was 13.9 months (95% CI, 7.5-NR); 1- and 2-year PFS were 57% and 36%. Grade 5 adverse events occurred in 8 patients (22%), including one possible (duodenal perforation), one probable (kidney injury with sepsis), and 6 unlikely/unrelated treatment-related deaths. Conclusions: Neoadjuvant DTP enables surgical resection in BRAF m-ATC compared with historical controls, and leads to improved PFS and OS. This approach should now be considered a standard of care for BRAF m-ATC. Clinical trial information: NCT04675710 . Total N=36 Age (y), median (range) 67 (46-86) Stage IVB/IVC, n (%) 15 (42%)/21 (58%) Best RECIST response neoadjuvant phase, n (%) CR 2 (6%) PR 24 (67%) SD 6 (17%) PD 4 (11%) Percent change target lesion diameter, mean (95% CI) -44% (-54%, -34%) Surgical morbidity score change, mean (95% CI) -1.7 (-2.1, -1.3)

Abstract The use of radiofrequency ablation (RFA) of benign, symptomatic thyroid nodules is growing in clinical practice. Objective outcomes of symptom relief are needed to support the use of this treatment. Thus, a previously established thyroid nodule symptom scoring system was prospectively administered to patients prior to RFA of symptomatic thyroid nodules and then at 1, 3, 6, and 12 months following ablation. A total of 38 patients of mean age 57 years were treated with RFA between August 2022 and January 2024 and completed at least 1 follow-up survey. Five of these patients underwent simultaneous ablation of 2 thyroid nodules; the remainder had a single nodule treated. Mean modified symptom score prior to RFA was 3.5 (SD 1.6) with higher scores correlating with increasing baseline nodule volume (R = 0.46, P = 0.0038). Patient symptom scores decreased at the first 1-month survey (mean 1.2; SD 1.3) and 3-month survey (mean 0.9; SD 1.3) with durable response in those patients with more extended follow-up. In those patients with imaging follow-up, decreasing nodule size was shown to correlate with decreasing symptoms. The early results of this study show that RFA of benign, symptomatic thyroid nodules results in quantifiable symptom relief within 3 months of treatment. Such objective measures of symptom relief may be used to measure long-term durability of treatment.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell–engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

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 Background The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. Methods We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed‐carboplatin (PC) at Mayo Clinic since 2019. Results Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC ( n = 7) had durable responses with a median progression‐free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. Conclusions This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

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