Publications by authors named "Bryan R Haugen"

Importance: A subset of thyroid cancers develops in a setting of a known hereditary cancerassociated syndrome. Understanding the population prevalence of thyroid cancer-associated syndromes is important to guide germline genetic testing and clinical management.

Objective: To estimate the prevalence of the major thyroid cancer-associated syndromes in the United States using the All of Us Research Program (AoU) data.

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Background: The primary treatment for locoregional recurrent/persistent differentiated thyroid cancer (DTC) is repeated lymph node dissection; however, there are limited reports on the safety and long-term efficacy of multiple operations.

Methods: Patients who underwent a cervical lymph node dissection between 1998 and 2022 were included in this study. Demographics, initial thyroid surgery, subsequent lymph node dissections, follow up information, and response to therapy were acquired.

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Article Synopsis
  • Lenvatinib, a multikinase inhibitor, is effective in improving progression-free survival (PFS) in patients with radioiodine-refractory differentiated thyroid cancer, leading to a study on its combination with pembrolizumab.
  • The study enrolled two groups: naïve patients to multikinase inhibitors and those who progressed on lenvatinib, with results showing a 65.5% overall response rate in naïve patients but only 16% in those who previously had lenvatinib.
  • Findings suggest that the combination therapy may improve treatment durability for naïve patients and could serve as a potential salvage option for those whose cancer progressed on lenvatinib alone.
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  • * Evidence shows that oncocytic thyroid carcinoma has distinct genetic changes compared to other thyroid cancers, displaying higher rates of somatic gene variants and unique mitochondrial DNA variations.
  • * The cancer presents a greater likelihood of lymph node metastases and distant metastases than follicular and papillary thyroid carcinomas, and it has a lower tendency to absorb radioiodine for treatment.
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Estrogen receptor (ER) α expression and associated signaling is a major driver of over two-thirds of all breast cancers (BC). ER targeting strategies are typically used as a first-line therapy in patients with steroid receptor positive (SR+) disease. Secondary resistance to anti-estrogenic agents may occur with clonal expansion and disease progression.

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Background: Most patients diagnosed with thyroid cancer have low-risk disease, but some have a higher risk for persistent or recurrent disease and even death from thyroid cancer. Few studies have evaluated potential anthropometric, lifestyle, or dietary risk factors for advanced or aggressive types of thyroid cancer.

Methods: Using data from a large US cohort study, we examined associations for high-risk thyroid cancer (HRTC) and, separately, low-risk thyroid cancer (LRTC) in relation to anthropometric factors, diet, smoking, and alcohol consumption.

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Context: Thyroid nodule ultrasound-based risk stratification schemas rely on the presence of high-risk sonographic features. However, some malignant thyroid nodules have benign appearance on thyroid ultrasound. New methods for thyroid nodule risk assessment are needed.

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Thyroid hormone replacement with levothyroxine (LT4) is a recommended treatment for patients undergoing thyroidectomy. The starting LT4 dose is frequently calculated based on the patient's weight. However, the weight-based LT4 dosing performs poorly in clinical practice, with only ∼30% of patients achieving target thyrotropin (TSH) levels at the first thyroid function testing after treatment initiation.

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  • A comprehensive genomic analysis was conducted on a large number of thyroid nodules (50,734 FNA samples) to identify molecular alterations and better understand their clinical significance, particularly in Bethesda categories III-VI.
  • The results showed that a majority (65.3%) of the samples tested negative for significant alterations, while a smaller proportion (33.9%) tested positive, revealing different mutation patterns in BCIII-IV and BCV-VI nodules, with BCV-VI showing more aggressive genetic changes.
  • The findings indicate that 68% of BCIII-IV nodules were negative, highlighting the potential to avoid unnecessary surgery, while BCV-VI nodules had more actionable mutations that could inform treatment decisions for patients.
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The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines.

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The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC.

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Combination therapy with lenvatinib plus programmed death-1 (PD-1) immune checkpoint blockades (ICBs) is under investigation in many solid tumors, including thyroid cancer. Lenvatinib is known to reduce angiogenesis and may overturn the immunosuppressive effects of vascular endothelial growth factor in the tumor microenvironment. Previous studies investigating the effects of VEGF receptor inhibition on the immune response were performed in rapidly growing tumor models where immune equilibrium is not established before treatment.

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Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs.

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The treatment of differentiated thyroid cancer continues to move away from a 'one size fits all' approach to a process of tailored therapeutic decision-making that incorporates disease-specific factors and individual patient preferences. Management options range from active surveillance to thyroid lobectomy to total thyroidectomy with or without the use of postoperative radioactive iodine (RAI). RAI may be administered for one or more reasons: Thyroid remnant ablation, adjuvant therapy, or therapy for persistent structural disease.

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Purpose: Thyroid disease is a frequent comorbidity in women with breast cancer, and many require thyroid hormone replacement therapy (THRT). We postulated that THRT has a deleterious clinical effect mechanistically through hormonal interactions, nuclear receptor cross-talk, and upregulation of high-risk breast cancer genes.

Experimental Design: Observational studies of patients with lymph node-negative (LN) breast cancer ( = 820 and = 160) were performed to test interactions between THRT and clinical, histologic, outcome, and treatment variables.

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Despite advances in targeted kinase inhibitor development for patients with medullary thyroid cancer (MTC), most patients develop resistance and would benefit from alternative approaches. Immune-based therapies are now considered for patients with progressive MTC. This study is the first comprehensive assessment of the immune milieu, immune-suppressive molecules, and potential tumor antigens in patients with MTC.

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The 2015 American Thyroid Association (ATA) clinical practice guidelines (CPGs) on management of thyroid nodules (TNs) and differentiated thyroid cancer (DTC) in adults were developed to inform clinicians, patients, researchers, and health policy makers about the best available evidence, and its limitations, relating to management of these conditions. We conducted a cross-sectional electronic survey of ATA members' perspectives of these CPGs, using a standardized survey (Clinician Guidelines Determinant Questionnaire) developed by the Guidelines International Network. A survey link was electronically mailed to members in February of 2019, with reminders sent to nonrespondents 2 and 5 weeks later.

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Purpose: Thyroid cancer cell lines are valuable models but have been neglected in pancancer genomic studies. Moreover, their misidentification has been a significant problem. We aim to provide a validated dataset for thyroid cancer researchers.

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Cancer cell lines are critical models to study tumor progression and response to therapy. In 2008, we showed that approximately 50% of thyroid cancer cell lines were redundant or not of thyroid cancer origin. We therefore generated new authenticated thyroid cancer cell lines and patient-derived xenograft (PDX) models using and feeder cell approaches, and characterized these models and .

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The historical management approach for many patients with indeterminate thyroid nodule fine needle aspiration cytology is a diagnostic lobectomy or thyroidectomy. However, the majority of patients undergo surgery unnecessarily, because most are proven to have benign disease on histology. Molecular testing is a diagnostic tool that can be used to help guide the clinical management of thyroid nodules with indeterminate cytology results.

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Background: Care for patients with thyroid nodules is complex and multidisciplinary, and research demonstrates variation in care. The objective was to develop clinical guidelines and quality metrics to reduce unwarranted variation and improve quality.

Methods: Multidisciplinary expert consensus and modified Delphi approach.

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Article Synopsis
  • About 20% of fine-needle aspirations (FNAs) of thyroid nodules yield indeterminate results, often classified under Bethesda categories III or IV, and diagnosing these nodules accurately can potentially reduce unnecessary surgeries.
  • A study was conducted involving 782 patients with 1013 thyroid nodules to assess the effectiveness of a multigene classifier test (ThyroSeq v3) in distinguishing benign from malignant nodules.
  • The results showed that the test had a high sensitivity of 94% and a specificity of 82%, with a negative predictive value of 97%, effectively identifying benign nodules and helping to prevent surgery in low-risk cases.
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Objective: The second edition Bethesda System for Reporting Thyroid Cytology estimates 6%-18% malignancy rate of category III (B3) and 10%-40% for category IV (B4) nodules; however, reported malignancy rates have considerable variability among institutions. Use of molecular classifiers (including Afirma Gene Expression Classifier, GEC) can be utilized in management of thyroid nodules. Our objective was to analyse malignancy rates of B3 and B4 nodules and determine clinical outcomes of GEC Benign nodules.

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