Meeting Program and Abstracts
2023; Mary Ann Liebert, Inc.; Volume: 33; Issue: S1 Linguagem: Inglês
10.1089/thy.2023.29156.abstracts
ISSN1557-9077
Tópico(s)Thyroid Disorders and Treatments
ResumoThyroidVol. 33, No. S1 American Thyroid Association 2023 Annual MeetingFree AccessMeeting Program and AbstractsPublished Online:15 Sep 2023https://doi.org/10.1089/thy.2023.29156.abstractsAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail 2023 AMERICAN THYROID ASSOCIATION ANNUAL & CENTENNIAL CELEBRATION MEETING PROGRAMWednesday, September 27, 2023TimeEvent7:00 AM – 4:30 PMEndocrine Neck Advanced Ultrasound Course (additional registration fee)7:30 AM – 3:00 PMLeadership Development Workshop (additional registration fee)8:45 AM – 4:00 PMInterventional Endocrinology Workshop (additional registration fee)9:00 AM – 5:00 PME. Chester Ridgway Trainees Conference1:00 PM – 5:45 PMRegistration Open3:30 PM – 5:30 PMATA Committee and Task Force MeetingsAfter 5:30 PMNetworking/Dinner on Your OwnThursday, September 28, 20237:00 AM – 5:45 PMRegistration Open7:30 AM – 9:00 AMPlenary Session & Presidential Address • Opening Remarks • Year in Thyroidology9:00 AM – 10:00 AMHighlighted Oral Abstracts10:00 AM – 10:30 AMPoster Review & Refreshment Break10:00 AM – 6:15 PMExhibit Hall Open10:35 AM – 11:35 AMSymopsia • Thyroid Subclinical Disease and Cardiovascular Risk • Understand Current Evidence for Redifferentiation Therapy • Social Media for the Social Thyroidologist • Deiodinases in Developmental Transitions and Thyroid Disorders11:35 AM – 12:45 PMPoster ReviewLunch on Your Own11:45 AM – 12:45 PMExpo Theater Presented by Acella Pharmaceuticals, LLC: Changing the Paradigm of Hypothyroidism Treatment: Two Researchers' Perspectives12:55 PM – 1:45 PMSidney H. Ingbar Distinguished Lectureship Award and Lewis E. Braverman Distinguished Lectureship Award Celebration & Lectures • Rosalind Brown. MD – Thyroid Disease in Children: A Fifty‐Year Perspective • Yaron Tomer, MD ‐ The Role of Autophagy in Autoimmune Thyroiditis: A New Paradigm1:50 PM – 2:50 PMOral Abstract Sessions • #1: Thyroid Cancer • #2: TH Action and Regulation • #3: Effects and Treatment of Autoimmune Thyroid Disease3:00 PM – 4:00 PMExpo Theater Presented by Horizon Therapeutics: Thyroid Eye Disease (TED): Early Diagnosis, Referral, and Treatment with TEPEZZA Diversity, Equity and Inclusion Networking Session Exhibitor Networking Break E. Chester Ridgway Trainee Conference: Basics of Thyroid Ultrasound (Trainees Only)4:10 PM – 5:10 PMSawin Lecture – The American Thyroid Association 1923 – 2023, Honoring our Past – Embracing our Future5:15 PM – 6:15 PMBobbi Smith Networking Social Hour – Celebrating ATA's CentennialAfter 6:15 PMNetworking/Dinner on Your Own Friday, September 29, 20237:00 AM – 7:45 AMThyroid & Pregnancy Guidelines Update7:00 AM – 5:00 PMRegistration Open7:50 AM – 9:50 AMPlenary Session • Morning Announcements & Recognition of The John B. Stanbury Thyroid Pathophysiology Medal, Distinguished Service & Women in Thyroidology (WIT) Woman of the Year Awardees ‐ Carole Anne Spencer, PhD ‐ John B. Stanbury Thyroid Pathophysiology Medal ‐ M. Regina Castro, MD – Distinguished Service Award ‐ Lisa Orloff, MD – Women in Thyroidology (WIT) Woman of the Year • Innovations in Research: Conversations for the Future • Van Meter & Valerie Anne Galton Lectureship Award Celebration & Lectures ‐ Anne R. Cappola, MD, Sc.M – Defining Thyroid Dysfunction: A Collaborative Approach • Van Meter Award Announcement9:50 AM – 10:20 AMPoster Review and Refreshment Break9:50 AM – 4:00 PMExhibit Hall Open10:20 AM – 11:20 AMSymposia • Endocrine Disrupting Chemicals and the Thyroid: High Time to Act • Clinical Application of Updated ATA Guidelines and ACR‐TIRADS: Value and Limitations of Sonographic Assessment of Thyroid Nodules • Quality of Life in Patients with Thyroid Disease • The Use of Thyroid Analogues in the Treatment of Non‐Thyroidal Disease11:20 AM – 12:40 PMPoster ReviewLunch on Your Own11:30 AM – 12:30 PMExpo Theater Presented by Exelixis: An Exelixis Product for the Clinical Management of Appropriate Patients in Differentiated Thyroid Cancer11:30 AM – 12:15 PMMeet the NIDDK Program Directors12:40 PM – 1:40 PMOral Abstract Sessions • #4: Thyroid Cancer • #5: Surgery • #6: Thyroid Hormone Action and Regulation1:50 PM – 2:50 PMSymposia • How Can Neonatal Screening Keep Up with Genetic Defects? • Thyroid Hormone Mood and Cognition • AI Chatbots – Ethical & Practical Implications • Managing Low Risk Thyroid Cancers – What's the Right Answer in 2023?2:50 PM – 4:00 PMExhibitor Networking & Refreshment Break2:50 PM – 5:15 PMATA Surgical Symposium – Controversies in Thyroidology: Value and Challenges of Multidisciplinary Team Approach ▪ Panel 1 – Case Discussions: Early Cancers and Nodules with Mutations ▪ Panel 2 – Case Discussions: Advanced Differentiated and Medullary Thyroid Cancer3:00 PM – 4:00 PMExpo Theater Presented by Sonic Healthcare: Molecular Fingerprinting of Bethesda III‐VI Thyroid Nodules by ThyroSeq Detects Over 100 Unique Profiles: A Roadmap for Optimizing Patient Management Special Interest Networking Sessions • Artificial Intelligence Networking Session • Animal Models/Basic Science Meet Up E. Chester Ridgway Trainee Conference: Bench to Bedside Case Presentations: Hypothyroidism Case and Hyperthyroidism Case (Trainees Only)4:05 PM – 4:50 PMDiscussion‐Debates/MTP Workshops • Cancer Syndrome with Non‐Medullary Thyroid Cancer • Impact of Drugs on Thyroid Physiology • Change in Treatment of Hyperthyroidism Over the Century • New omic Approaches in Understanding Thyroid Disease5:00 PM – 6:00 PMExpo Theater Presented by Bayer: The Clinical Role of VITRAKVI (larotrectinib): Presentation for Thyroid Specialists on NTRK Gene Fusions in Thyroid Cancer5:15 PM – 5:45 PMATA Annual Membership Meeting (Formerly Annual Business Meeting)Members OnlyAfter 5:45 PMNetworking/Dinner on Your Own Saturday, September 30, 20237:00 AM – 5:00 PMRegistration Open7:00 AM – 7:45 AMProgram Directors & Division Chief Networking Session7:45 AM – 9:50 AMPlenary Session • Morning Announcements from Co‐Chairs • Keyonte: Diversity, Equity and Inclusion in Medicine & Academics: Reflections & A Call to Action • Women in Thyroidology Plenary & Recognition of Women Advancing Thyroid Research Award Recipients9:50 AM – 1:00 PMExhibit Hall Open9:50 AM – 10:20 AMPoster Review and Refreshment Break10:25 AM – 11:25 AMSymposia • Research Grant Session • Thyroid and Aging, Treatment in Older Adults • Treatment of ATA Intermediate Risk DTC • The Roles of Autophagy and Thyroid Hormone in the Pathogenesis and Treatment of NAFLD11:25 AM – 12:40 PMPoster Review and Lunch on Your Own11:30 AM – 12:30 PMExpo Theater Presented by Loxo@Lilly: Retevmo: Precision Oncology for Patients with RET‐Positive Thyroid Cancer Multicenter Clinical Trials Networking Session12:40 PM – 1:40 PMPlenary Session ‐ Artificial Intelligence1:50 PM – 2:50 PMExpo Theater Presented by Qualisure Diagnostics Inc.: Making Treatment Decisions Using a Novel Genomic Classifier for Papillary Thyroid Cancer Oral Abstract Sessions • #7: Technology & Thyroid • #8: Thyroid Nodules and Goiter • #9: Quality of Life & Health Disparities2:00 PM – 5:00 PMATA Pediatric Thyroid Symposium ▪ Percutaneous Approaches to Neoplastic Thyroid Disease in Children: Who and When? ▪ Pediatric Tumor Board ▪ Managing Children with Moderate Risk MEN2A3:00 PM – 3:50 PMHighlighted Poster Sessions • #1: Thyroid Cancer & Surgery • #2: Thyroid Cancer, Pregnancy & Development, Health Disparities / Health Equity • #3: Disorders of Thyroid Function, TH Action, Metabolism and Regulation, Thyroid Imaging4:05 PM – 4:50 PMDiscussion‐Debates/MTP Workshops • Oncocytic Tumors – New Definition and How They Differ from Previous Classifications • Management of Patients with Thyroid Disorders Undergoing IVF • Tumor Vulnerability: Rationale for Combined Therapy in BRAFV600E Thyroid Cancers5:00 PM – 8:00 PMNetworking/Dinner on Your Own 8:00 PM – 11:00 PMATA Centennial Celebration Party (Additional registration required) Join us for an evening of dancing, games and karaoke as we celebrate the ATA's Centennial. Party refreshments and snacks will be served.Sunday, October 1, 20238:00 AM – 11:00 AMRegistration Open8:15 AM – 9:15 AMParallel Sessions • Tumor Board • Genetic Defects in Humans and Mice Affecting Thyroid Function9:15 AM – 11:15 AMParallel Sessions • Arthur Bauman Symposium – Insights Into the New ATA Guidelines • Basic/Translational Symposium ▪ Recent Progress on the Effect of Thyroid Hormone Signaling in Development in Animal Models ▪ Thyroid Hormone TransportersTHURSDAY, SEPTEMBER 28, 2023HIGHLIGHTED ORAL 1Autoimmunity Clinical Highlighted OralTHE USE OF MEDICAL THERAPY FOR THYROID EYE DISEASE IN THE ERA OF TEPROTUMUMABKharisa Rachmasari*, David Toro‐Tobon, Lilly Wagner, Andrea Tooley, Layla Abdul Jabbar, Marius StanMayo Clinic Rochester, USAObjective: Teprotumumab was approved for thyroid eye disease (TED) by the Food and Drug Administration (FDA) in January 2020. This study investigates clinical practice changes before and after Teprotumumab era.Methods: A retrospective review was conducted on adult patients with TED who were treated in a multicenter health system between 2018 and 2022. Demographics, clinical characteristics, disease activity based on clinical activity score (CAS), proptosis, diplopia, disease severity based on EUGOGO classification, treatment choice and types of insurance were analyzed.Results: A total of 74 patients with active, moderate to severe TED were identified, 33 received Teprotumumab, 19 corticosteroids, 8 Tocilizumab, and 14 patients did not receive medical therapy despite medical recommendation. Of 74 medical recommendations, around half (n = 39; 52.7%), were made collaboratively by endocrinologist and ophthalmologist in a specialized TED clinic. Prior to Teprotumumab availability, 18 patients were recommended medical therapy, of dwhich the majority received corticosteroids (n = 13) while the rest received Tocilizumab (n = 5). After Teprotumumab became available, 56 patients were recommended medical therapy: the majority (n = 33) received Teprotumumab, 6 corticosteroids, 3 Tocilizumab, while 14 patients did not receive medical therapy. All these 14 patients were advised for Teprotumumab. The most frequent factors contributing to the discordance between physicians' recommendations and therapy received were patients' refusal (n = 7) and insurance denial (n = 3). Of 7 patients who refused medical therapy, 5 patients declined due to side effects concerns. Our safety analysis of patients who ultimately received therapy indicates that Teprotumumab was associated with weight loss (27.3%), otic changes (27.3%), and hyperglycemia (18.2%), while corticosteroids were associated with insomnia (15.8%). Furthermore, one patient in the Teprotumumab group developed sepsis and one patient in the Tocilizumab group had an infusion reaction requiring urgent hospitalization.Conclusion: In the era of Teprotumumab, more patients with active, moderate‐severe TED were evaluated for medical therapy. However, this did not translate into every evaluated patient receiving the recommended medical treatment, mainly due to safety concerns and accessibility of the medication. Efforts to address these challenges should focus on the identification of risk factors for adverse effects and health care policy adjustments.HIGHLIGHTED ORAL 2Iodine Uptake and Metabolism Clinical Highlighted OralASSESSMENT OF IODINE STATUS IN U.S. WOMEN OF REPRODUCTIVE AGE AND PREGNANT WOMEN: NHANES 2001‐2020Cheng Han*, Sun Lee, Carol Peng, Elizabeth PearceBoston University Chobanian & Avedisian School of Medicine, USABackground: Iodine is an essential micronutrient required for the synthesis of thyroid hormones, which are critical for fetal brain development and growth. Iodine deficiency during pregnancy can lead to adverse outcomes including child cognitive impairment. We aimed to evaluate recent trends in urinary iodine concentration (UIC) levels in U.S. women of reproductive age and pregnant women, using data from the NHANES database.Methods: Representative samples of U.S. reproductive age and pregnant women were enrolled in NHANES 2001–2020 across 5 cycles: 2001–2004, 2005–2008, 2009–2012, 2013–2016, and 2017–2020. There were 24,145 reproductive age women and 1,702 pregnant women available for analysis. Descriptive data are provided. We used linear regression models to investigate associations between UIC and potential contributing factors.Results: The median UIC levels in reproductive age women have declined from 142 μg/L to 106 μg/L (P < 0.001). Median UIC values in pregnant women remained relatively stable over the study period, ranging from 147 μg/L to 133 μg/L (Pfor trend = 0.68). Linear regression analysis indicate that UIC is significantly positively related with dairy consumption and inversely associated with education level and socioeconomic status in reproductive age women. UIC is only positively related with dairy consumption in pregnant women.Conclusions: The study uncovered a worrying decline in UIC levels in reproductive age women in the US over the last two decades. While the UIC remained stable in pregnant women, it still falls below the WHO's recommended criterion of 150 μg/L for iodine deficiency during pregnancy. The findings of the study emphasize the importance of taking measures to ensure sufficient iodine intake among reproductive age women and during pregnancy.HIGHLIGHTED ORAL 3Thyroid Cancer Basic Highlighted OralTET2‐MUTANT CLONAL HEMATOPOIESIS DRIVES RESISTANCE TO MAPK INHIBITORS IN BRAFV600E ‐MUTANT ANAPLASTIC THYROID CANCERVera Tiedje*1, Pablo Sánchez Vela1, Avi Srivastava2, Brian Untch3, Laura Boucai3, Stephanie Lobagouh3, Sebastiá Franch Expósito3, Tianyue Qin3, Aishwarya Krishnan1, Anthony Martinez Benitez3, Jillian Greenberg4, Gnana Krishnamoorthy3, Kelly Bolton5, Ahmet Zehir3, Rahul Satija2, Robert Bowman3, Jeffrey Knauf3, Sean Devlin3, Larry Norton3, Michael Berger3, Ross Levine3, James Fagin31Memorial Sloan Kettering Cancer Center, USA,2New York Genome Center, USA,3Memorial Sloan Kettering Cancer Center, USA,4Memorial Sloan Kettering Cancer Center, USA,5Washington University School of Medicine, USABackground/Objective: BRAFV600E‐mutant anaplastic thyroid cancers (ATCs) are heavily infiltrated with myeloid cells. Combined BRAF/MEK inhibition has shown remarkable responses in BRAFV600E‐mutant ATCs. Clonal Hematopoiesis (CH) is caused by increased fitness of hematopoietic stem‐progenitors conferred by somatic mutations in genes such as the epigenetic modifier TET2, leading to overrepresentation of mutant clones in blood, especially among myeloid cells. The incidence of CH increases with age and radiation exposure and is a risk factor for hematologic malignancies, atherosclerosis and other comorbid conditions of aging. Thyroid cancers are the most common tumor associated with CH. CH is associated with worse outcomes in other solid tumor patients, although the specific consequences of CH on therapy response are unknown.Methods: We annotated the MSK‐IMPACT cohort and generated mouse models with concurrent CH and ATC. We performed competitive bone marrow transplants (bmt) from tamoxifen‐treated C57BL/6J CD45.2+ mice harboring a HSPC‐specific recombinase (SclCreERT) and a TdTomato reporter to specifically delete and identify excised Tet2 cells into irradiated CD45.1+ mice. After engraftment mice were injected orthotopically with BrafV600E/Tp53‐/‐ (TBP3743) ATC cells. Mice were treated with dab/tram vs vehicle. Multispectral flow cytometry and CITE‐scRNASeq analysis was performed.Results: CH was associated with decreased overall survival in thyroid cancer patients, including ATC. In our murine models Tet2‐/‐ CD45+ cells were enriched in the TME relative to peripheral blood ‐ primarily monocytes, macrophages and dendritic cells. Tumor growth in vehicle conditions did not differ. Dab/tram significantly inhibited tumor size assessed by ultrasound after 1‐ and 2‐week treatment compared to baseline in Wt, but not in Tet2‐/‐ bmt mice, indicative of MAPKi resistance in ATCs infiltrated with Tet2‐mutant clones. Dab/tram failed to fully inhibit MAPK transcriptional output in Tet2‐/‐ vs WT bmt mice. Instead, aberrant Jak‐Stat, VEGF, and hypoxia signatures were seen in tumor and Tet2‐/‐ myeloid cells. Tet2‐/‐ myeloid cells in dab/tram‐treated ATCs had increased expression of the chemokines Ccl2, Ccl6, Ccl7, Ccl9 and 12, which are lead candidate drivers of resistance to MAPK pathway blockade.Conclusions: CH‐mutations lead to resistance to dab/tram in murine ATC. Our work opens new avenues for the selective targeting of tumor‐promoting inflammation in ATC.HIGHLIGHTED ORAL 4Thyroid Nodules and Goiter Translational Highlighted OralRISK OF THYROID NODULES IN RESIDENTS OF UKRAINE EXPOSED AS CHILDREN OR ADOLESCENTS TO IODINE‐131 FROM THE CHORNOBYL ACCIDENTElizabeth Cahoon*1, Eric Grimm2, Kiyohiko Mabuchi1, Zhi‐Ming Mai1, Rui Zhang1, Vladimir Drozdovitch1, Maureen Hatch1, Mark Little1, Kamau Peters1, Tetiana Bogdanova3, Evgeniy Shelkovoy3, Viktor Shpak3, Galyna Terekhova3, Galyna Zamotayeva3, Ihor Pasteur3, Sergii Masiuk4, Mykola Chepurny4, Lydia Zablotska5, Robert McConnell6, Patrick O'Kane7, Mykola Tronko3, Alina Brenner11National Cancer Institute, USA,2University of Colorado School of Medicine, USA,3V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine, Ukraine,4National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Ukraine,5Department of Epidemiology & Biostatistics School of Medicine, University of California, San Francisco, USA,6Columbia University, USA,7Thomas Jefferson University Hospital, USAExternal exposure to ionizing radiation during childhood is one of the most established risk factors for thyroid cancer. However, the relationship between radioactive iodine 131 (I‐131) exposure and the development of thyroid nodules is not well‐characterized and risk estimates vary widely.The objective of this study is to evaluate the association between childhood I‐131 exposure and prevalence of ultrasound detected thyroid nodules overall and by the following case groups: nodule histology/cytology (neoplastic / suspicious / non‐neoplastic), size (<10 mm / ≥10 mm), and number (single / multiple).We assessed prevalence of thyroid nodules at first thyroid screening examination conducted in 1998‐2000 (median population age 21.5 years at screening) in residents of Ukraine aged <18 years at the time of the Chernobyl accident (April 26, 1986) with direct thyroid radioactivity measurements. Thyroid doses in Gray (Gy) ranged from 0.0003 Gy to 31 Gy with a mean of 0.53 Gy. Excess odds ratios (EOR) per Gy and 95% confidence intervals (95% CI) were estimated using logistic regression.Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. We found significant dose‐response based on a linear EOR model for each case group. However, consistent with downturn or flattening in category‐specific EORs at high doses, there was evidence of exponential departure from linearity for all thyroid nodules (p‐value = 0.02). Below 5 Gy, the dose‐responses were consistent with linearity for each case group and for all nodules, the EOR/Gy was 1.11 (95% CI: 0.65, 1.77). Among subjects with doses 1% in pembrolizumab‐treated patients. Median follow‐up: 102.0months (range:0.6‐102) DT; 28.0months (range:3‐63) DTP; 42.0months (range:7‐75) neoadjuvant. mOS was significantly different between DT and all other groups: 7.0months (95%CI,2.5–11.4) DT; 17.0months (95%CI,11.9–22.1) DTP; 63.0months (95%CI,15.6–110.3) neoadjuvant; (p < 0.001). 12‐/24‐month survival rates: 33.7%/28.9% DT; 60.2%/36.5% DTP; 81.6%/75.4% neoadjuvant. mPFS was also significantly longer with DTP (11.0months [95%CI,7.0–15.0]) compared to DT alone (4.0months [95%CI,0.7–7.3]) as initial treatment (p = 0.049). Response rate, defined as complete+partial responses, was 64.5% with DT and 73.3% with DTP. No grade 5 adverse events (AEs) occurred, but 32.4% had immune‐related AEs, most frequently colitis and hepatitis.Conclusions: Our results suggest that in BRAFm‐ATC, a multimodal approach including addition of pembrolizumab to DT, and surgical resection of the primary tumor after initial BRAF‐targeted therapy (in selected patients), may provide a significant survival benefit. However, conclusions are limited by the retrospective nature of the study and smaller number of patients in DT group. Additional prospective data are needed to confirm this observation.ORAL 6Thyroid Cancer Translational OralTHE IDENTIFICATION OF NOVEL GENETIC VULNERABILITIES IN ANAPLASTIC THYROID CANCER CELLS TO OVERCOME RESISTANCE TO BRAFV600E INHIBITOR USING A GENOME‐WIDE CRISPR SCREENHaojian Li1, Xiaolin Wu2, David Sun2, Urbain Weyemi1, Myriem Boufraqech*11NCI, USA,2Frederick National Laboratory for Cancer Research, USAObjective: Anaplastic thyroid cancer (ATC) cells are particularly resistant to most common therapeutic strategies. There are major gaps in our understanding of the mechanism of resistance in ATC cancer cells carrying BRAFV600E mutation. Most of the current targeted therapies using BRAFV600E inhibitors have failed, and the combination approach in which mutant BRAF inhibitors were coupled with other targeted therapies including TKI have shown limited efficacy in patients with advanced thyroid cancer. Therefore, there is an urgent need to identify new determinants of resistance to BRAFV600E inhibitors and filling these gaps will fundamentally reshape our approach to ATC treatment. Recent studies demonstrated that BRAFV600E ‐driven advanced and metastatic thyroid cancer are not sensitive to monotherapies with mutant BRAF inhibitors due to acquired resistance mediated by genetic alterations and/or activation of metabolic and oncogenic signaling pathways. Our overall hypothesis is that BRAFV600E ‐driven ATC cancer cells heavily rely on certain genes to survive most treatments targeting mutant BRAF, and CRISPR/Cas9‐based sgRNAs directed against these specific genes would enhance cell death by mutant BRAF inhibitors.Methods: To identify genetic vulnerabilities that sensitize ATC cancer cells to mutant BRAF inhibitors, we conducted a CRISPR‐based screen of genes linked to resistance to BRAF inhibitors and cancer cell survival. First, using BRAFV600E ‐driven ATC cell line 8505c, we harnessed a human CRISPR knockout library of 19,050 genes to identify genes whose loss enhances cell death by the BRAFV600E selective inhibitor Dabrafenib. Dabrafenib has a better toxicity profile compared to vemurafenib, and was recently approved by the FDA for the treatment of advanced and metastatic thyroid cancer. The human GeCKO v2 CRISPR library A that has 65,386 unique sgRNAs, targeting 19,052 protein‐coding genes, and 1864 microRNAs was used to generate mutant cells pool. These cells were then treated with Dabrafenib for 7 days, followed by genomic DNA extraction, PCR amplification, and Next Generation Sequencing.Results: Utilizing MAGeCKFlute pipeline analysis combined with transcriptomics profiling of cells exposed for 7 days to BRAFV600E inhibitor, we unveiled several essential genes required for survival upon dabrafenib treatment, among which mitochondrial stress genes are uniquely prominent. Our preliminary findings strongly suggest a key role for metabolic reprogramming in resistance to BRAFV600E inhibitors.Conclusion: We identified genetic determinants of resistance to mutant BRAF inhibitors. Our study unveils a unique understanding of how ATC cells survive upon BRAFV600E inhibitors treatment.ORAL 7Thyroid Cancer Clinical OralEFFICACY AND PREDICTORS OF RESPONSE TO RADIOACTIVE IODINE REDIFFERENTIATION THERAPY IN PREVIOUSLY IODINE REFRACTORY PAPILLARY THYROID CARCINOMASDavid Toro‐Tobon*, John Morris, Crystal Hilger, Candy Peskey, Jolanta Durski, Mabel RyderMayo Clinic, USAObjective: Redifferentiation therapy (RDT) variably restores radioactive iodine (RAI) avidity in patients with RAI refractory (RAIR) differentiated thyroid cancers (DTC). This study examined predictors of RAI avidity and overall outcomes in a subgroup of patients with papillary thyroid cancer (PTC) undergoing RDT.Methods: This is a retrospective review of 23 patients with RECIST‐progressive metastatic RAIR‐PTC who underwent RDT between 2017 and 2022 at Mayo Clinic. All received MEK inhibitor or combination BRAF‐MEK inhibitors for 4 weeks. Those with increased RAI avidity at week 3 (responders) received high‐dose I‐131 therapy.Results: 4 of 11 (36.3%) with classical PTC (C‐PTC), 2 of 4 (50%) with tall cell variant‐PTCs (TCV‐PTC), 4 of 4 (100%) with follicular variant‐PTCs (FV‐PTC), and 2 of 4 (50%) tall cell features‐PTCs (TCF‐PTC) had restored RAI avidity following RDT using dabrafenib/trametinib (7 BRAF mutant) or trametinib (4 RAS mutant). All 5 (100%) RAS mutant tumors (2 C‐PTC and 3 FV‐PTC) had restored RAI avidity compared to 7 (38.8%) of BRAF mutant tumors (2 C‐PTC, 2 TCV‐PTC, 2 TCF‐PTC, and 1 FV‐PTC). The median thyroglobulin was 211 mIU/L in responders and 46 mIU/L in nonresponders (p = 0.06). Patients with FV‐PTC (p = 0.03), RAS mutation (p = 0.01), distant metastasis (p = 0.05), no locoregional disease at initial staging (p < 0.01), bone metastasis (p = 0.03), prior radiotherapy (p = 0.01), or prior systemic therapy (p = 0.01) were more likely to have restored RAI avidity. The 12 responders received a median dose of 243.9 mCi. Regardless of I‐131 therapy, responders and non‐responders had similar RECIST objective responses (complete or partial response, stable disease, non‐complete response/non‐progressive disease) (81.8% and 80%, p = 0.9), median progression‐free survival (18 and 9 months, p = 0.45), overall survival (27 months and no mortality, p = 0.07), and time to any additional therapy (18 and 12 months, p = 0.9). Of the responders, 1 patient experienced histologic transformation to anaplastic thyroid cancer and 4 (17.3%) died.Conclusion: RDT restores RAI avidity in select patients with PTC, especially those with follicular and RAS phenotypes. RECIST responses were seen in both responders and non‐responders, with or without RAI therapy. Larger randomized studies are needed to confirm predictors of response and to objectively examine outcomes and safety.ORAL 8Thyroid Cancer Translational OralRATIONAL DRUG DESIGN OF VCP INHIBITORS TO ENHANCE NIS FUNCTION IN RADIOIODIDE THERAPYMartin Read*1, Ling Zha1, Katie Brookes1, Jana Kim2, Benjamin Small3,4, Merve Kocbiyik1, Selvambigai Manivannan1, Giovanni Bottegoni5,6, Liam Cox7, Vinodh Kannappan3,4, Weiguang Wang3,4, Kavitha Sunassee2, Philip Blower2, Hannah Nieto1, Vicki Smith1, Christopher McCabe11Institute of Metabolism and Systems Research, University of Birmingham, United Kingdom,2School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom,3Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, United Kingdom,4Disulfican Ltd, University of Wolverhampton Science Park, United Kingdom,5Institute of Clinical Sciences, University of Birmingham, United Kingdom,6Università degli Studi di Urbino Carlo Bo, Italy,7School of Chemistry, University of Birmingham, United KingdomObjective: New approaches are required to improve the efficacy of drugs that have the potential to enhance ablative radioiodide (RAI) uptake, especially in RAI‐refractory disease. Our recent experiments in multiple cellular models revealed that valosin‐containing protein inhibitors (VCPi), such as clotrimazole and disulfiram, markedly increase sodium iodide symporter (NIS) activity to promote
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