International Expert Consensus on US Lexicon for Thyroid Nodules.

Multiple US-based systems for risk stratification of thyroid nodules are in use worldwide. Unfortunately, the malignancy probability assigned to a nodule varies, and terms and definitions are not consistent, leading to confusion and making it challenging to compare study results and craft revisions. Consistent application of these systems is further hampered by interobserver variability in identifying the sonographic features on which they are founded. In 2018, an international multidisciplinary group of 19 physicians with expertise in thyroid sonography (termed the International Thyroid Nodule Ultrasound Working Group) was convened with the goal of developing an international system, tentatively called the International Thyroid Imaging Reporting and Data System, or I-TIRADS, in two phases: (phase I) creation of a lexicon and atlas of US descriptors of thyroid nodules and (phase II) development of a system that estimates the malignancy risk of a thyroid nodule. This article presents the methods and results of phase I. The purpose herein is to show what has been accomplished thus far, as well as generate interest in and support for this effort in the global thyroid community.

Durable tumor regression and restoration of neurologic function after treatment with anti-PD-1 in patients with functionally unresectable cutaneous squamous cell carcinoma with perineural spread into the cavernous sinus.

PURPOSE: To describe tumor response and cranial nerve function outcomes after administration of anti-PD-1 to patients with cutaneous squamous cell carcinoma (CSCC) with perineural spread to cranial nerves (CN) extending into the cavernous sinus. METHODS: Electronic patient records from a single institution were queried for patients with CSCC of the head and neck causing diplopia (ICD-10 H53.2) who were treated with anti-PD-1. Data extracted included demographics, duration of anti-PD-1 therapy, immune-mediated adverse reactions, tumor response per adapted RECIST v1.1, and changes in CN function and symptoms (e.g., pain). All patients were prescribed cemiplimab 350 mg IV q3 weeks. RESULTS: Four patients met inclusion criteria. They had varying degrees of pain and sensory deficits in branches of the trigeminal nerve (CN V). One, 2, 3 and 1 patients had baseline involvement of CN III, IV, VI and VII, respectively. MRI confirmed perineural cavernous sinus involvement in all patients. Duration of anti-PD-1 therapy ranged 15-60 weeks. All patients experienced an objective anti-tumor response to anti-PD-1; partial response n = 2, complete response n = 2. At a median follow-up of 22 months, responses were ongoing in all patients. All patients demonstrated improvement in ocular motility deficits and pain with resolution of symptoms in 3 and 1 patients, respectively. CONCLUSION: Administration of anti-PD-1 to patients with CSCC with perineural spread into the cavernous sinus can generate durable anti-tumor regressions and restore CN function, while sparing the morbidity associated with surgical resection and/or radiotherapy. Our findings add to emerging literature supporting this treatment approach for this patient population.

Clinician Agreement on the Classification of Thyroid Nodules Ultrasound Features: A Survey of 2 Endocrine Societies.

CONTEXT: Thyroid nodule risk stratification allows clinicians to standardize the evaluation of thyroid cancer risk according to ultrasound features. OBJECTIVE: To evaluate interrater agreement among clinicians assessing thyroid nodules ultrasound features and thyroid cancer risk categories. DESIGN, SETTING, AND PARTICIPANTS: We surveyed Endocrine Society and Latin American Thyroid Society members to assess their interpretation of composition, echogenicity, shape, margins, and presence of echogenic foci of 10 thyroid nodule cases. The risk category for thyroid cancer was calculated following the American College of Radiology-Thyroid Imaging Reporting & Data System (ACR-TIRADS) framework from individual responses. MAIN OUTCOMES AND MEASURES: We used descriptive statistics and Gwet's agreement coefficient (AC1) to assess the primary outcome of interrater agreement for ACR-TIRADS risk category. As secondary outcomes, the interrater agreement for individual features and a subgroup analysis of interrater agreement for the ACR-TIRADS category were performed (ultrasound reporting system, type of practice, and number of monthly appraisals). RESULTS: A total of 144 participants were included, mostly endocrinologists. There was moderate level of agreement for the absence of echogenic foci (AC1 0.53, 95% CI 0.24-0.81) and composition (AC1 0.54, 95% CI 0.36-0.71). The agreement for margins (AC1 0.24, 95% CI 0.15-0.33), echogenicity (AC1 0.34, 95% CI 0.22-0.46), and shape assessment (AC1 0.42, 95% CI 0.13-0.70) was lower. The overall agreement for ACR-TIRADS assessment was AC1 0.29, (95% CI 0.13-0.45). The AC1 of ACR-TIRADS among subgroups was similar. CONCLUSIONS: This study found high variation of judgments about ACR-TIRADS risk category and individual features, which poses a potential challenge for the widescale implementation of thyroid nodule risk stratification.

An International Survey on Utilization of Five Thyroid Nodule Risk Stratification Systems: A Needs Assessment with Future Implications.

Background: Multiple ultrasound-based risk stratification systems (RSSs) for thyroid nodules are used worldwide. Variations in structure, performance, and recommendations are confusing for physicians and patients and complicate management decisions. The goal of this study was to determine the factors that are associated with choice of RSS and barriers to RSS use. These results are intended to inform development of a universal international thyroid ultrasound RSS. Methods: An online survey with questions about usage of RSSs, ultrasound practice and volumes, training, specialty, practice type, and geographic region was made available to members of five professional societies via email. Subgroup analysis was performed to identify the factors that governed use of one or more of five leading RSSs: American Association of Clinical Endocrinology (AACE), American College of Endocrinology (ACE), and Associazione Medici Endocrinologi (AME) Medical Guidelines, American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), American Thyroid Association (ATA) guidelines, European Thyroid Association TIRADS (EU-TIRADS), and Korean Society of Thyroid Radiology/Korean Thyroid Association TIRADS (K-TIRADS). Results: There were 875 respondents from 52 countries (response rate not estimated due to overlapping society membership). More than 7 specialties were represented, with most (538; 61.5%) in endocrinology. The choice of RSS was strongly associated with medical specialty and geographic region. Of 692 respondents who indicated that their practice used an RSS, 213 (30.8%) used more than one. The specialties that were more likely to use multiple RSSs were surgery and others (40%), followed by endocrinology (33.0%), and radiology or nuclear medicine (17%) (p < 0.001). Of 271 (31.0%) respondents who indicated that they do not personally use an RSS, the majority (168; 62%) preferred to describe the specific sonographic characteristics/features that they believe are most relevant in a nodule. Conclusions: Almost one third of respondents indicated use of more than one RSS in their practice, potentially leading to confusion, and a similar proportion reported not using an RSS for various reasons. A unified international system that addresses their concerns and simplifies risk classification of thyroid nodules may benefit practitioners and patients. This is particularly important as newer thyroid nodule management options gain acceptance.

The Radiology Lecture Exchange (RALEX): A Virtual Visiting Professorship Platform for All.

Visiting Professorships (VPs) have significant benefits for both the guest lecturer and host institution. Such opportunities increase knowledge dissemination, research collaboration, opportunities for junior faculty members, and educational material that shores up perceived weaknesses in the host institution's training program. While VPs provide these benefits, such invitations are often costly due to travel and accommodation expenses, which can be challenging for host institutions. The COVID-19 pandemic - with the forced social and work distancing - has mandated that radiologists rethink how they interact and collaborate within their department and also within the larger medical and radiology communities. Virtual platforms have become critical for communication and education, and in this altered academic environment have provided an opportunity for us to redesign how VPs are designed. The virtual VP removes many of the cost and time burdens associated with travel and even enables greater communication where it might not have been economically or time-feasible. We present a virtual Microsoft Teams (Redmond, WA) based platform for facilitating VPs in all subspecialties and for all ranks called the Radiology Lecture Exchange.

ACR Appropriateness Criteria® Parathyroid Adenoma.

Hyperparathyroidism is defined as excessive parathyroid hormone production. The diagnosis is made through biochemical testing, in which imaging has no role. However, imaging is appropriate for preoperative parathyroid gland localization with the intent of surgical cure. Imaging is particularly useful in the setting of primary hyperparathyroidism whereby accurate localization of a single parathyroid adenoma can facilitate minimally invasive parathyroidectomy. Imaging can also be useful to localize ectopic or supernumerary parathyroid glands and detail anatomy, which may impact surgery. This document summarizes the literature and provides imaging recommendations for hyperparathyroidism including primary hyperparathyroidism, recurrent or persistent primary hyperparathyroidism after parathyroid surgery, secondary hyperparathyroidism, and tertiary hyperparathyroidism. Recommendations include ultrasound, CT neck without and with contrast, and nuclear medicine parathyroid scans. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Establishing ADC-Based Histogram and Texture Features for Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinoma.

The purpose of this study was to assess baseline variability in histogram and texture features derived from apparent diffusion coefficient (ADC) maps from diffusion-weighted MRI (DW-MRI) examinations and to identify early treatment-induced changes to these features in patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive chemoradiation. Patients with American Joint Committee on Cancer Stage III-IV (7th edition) HNSCC were prospectively enrolled on an IRB-approved study to undergo two pre-treatment baseline DW-MRI examinations, performed 1 week apart, and a third early intra-treatment DW-MRI examination during the second week of chemoradiation. Forty texture and six histogram features were derived from ADC maps. Repeatability of the features from the baseline ADC maps was assessed with the intra-class correlation coefficient (ICC). A Wilcoxon signed-rank test compared average baseline and early treatment feature changes. Data from nine patients were used for this study. Comparison of the two baseline ADC maps yielded 11 features with an ICC ≥ 0.80, indicating that these features had excellent repeatability: Run Gray-Level Non-Uniformity, Coarseness, Long Zone High Gray-Level, Variance (Histogram Feature), Cluster Shade, Long Zone, Variance (Texture Feature), Run Length Non-Uniformity, Correlation, Cluster Tendency, and ADC Median. The Wilcoxon signed-rank test resulted in four features with significantly different early treatment-induced changes compared to the baseline values: Run Gray-Level Non-Uniformity (p = 0.005), Run Length Non-Uniformity (p = 0.005), Coarseness (p = 0.006), and Variance (Histogram) (p = 0.006). The feasibility of histogram and texture analysis as a potential biomarker is dependent on the baseline variability of each metric, which disqualifies many features.

Comparison of Thyroid Risk Categorization Systems and Fine-Needle Aspiration Recommendations in a Multi-Institutional Thyroid Ultrasound Registry.

OBJECTIVES: The aim of this study was to compare how often fine-needle aspiration (FNA) would be recommended for nodules in unselected, low-risk adult patients referred for sonographic evaluation of thyroid nodules by ACR Thyroid Imaging Reporting and Data System (TI-RADS), the American Thyroid Association guidelines (ATA), Korean Thyroid Imaging Reporting and Data System (K-TIRADS), European Thyroid Imaging Reporting and Data System (EU-TIRADS), and Artificial Intelligence Thyroid Imaging Reporting and Data System (AI-TIRADS). METHODS: Seven practices prospectively submitted thyroid ultrasound reports on adult patients to the ACR Thyroid Imaging Research Registry between October 2018 and March 2020. Data were collected about the sonographic features of each nodule using a structured reporting template with fields for the five ACR TI-RADS ultrasound categories plus maximum nodule size. The nodules were also retrospectively categorized according to criteria from ACR TI-RADS, the ATA, K-TIRADS, EU-TIRADS, and AI-TIRADS to compare FNA recommendation rates. RESULTS: For 27,933 nodules in 12,208 patients, ACR TI-RADS recommended FNA for 8,128 nodules (29.1%, 95% confidence interval [CI] 0.286-0.296). The ATA guidelines, EU-TIRADS, K-TIRADS, and AI-TIRADS would have recommended FNA for 16,385 (58.7%, 95% CI 0.581-0.592), 10,854 (38.9%, 95% CI 0.383-0.394), 15,917 (57.0%, 95% CI 0.564-0.576), and 7,342 (26.3%, 95% CI 0.258-0.268) nodules, respectively. Recommendation for FNA on TR3 and TR4 nodules was lowest for ACR TI-RADS at 18% and 30%, respectively. ACR TI-RADS categorized more nodules as TR2, which does not require FNA. At the high suspicion level, the FNA rate was similar for all guidelines at 68.7% to 75.5%. CONCLUSION: ACR TI-RADS recommends 25% to 50% fewer biopsies compared with ATA, EU-TIRADS, and K-TIRADS because of differences in size thresholds and criteria for risk levels.

Analysis of Malignant Thyroid Nodules That Do Not Meet ACR TI-RADS Criteria for Fine-Needle Aspiration.

OBJECTIVE. Compared with other guidelines, the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) has decreased the number of nodules for which fine-needle aspiration is recommended. The purpose of this study was to evaluate the characteristics of malignant nodules that would not be biopsied when the ACR TI-RADS recommendations are followed. MATERIALS AND METHODS. We retrospectively reviewed a total of 3422 thyroid nodules for which a definitive cytologic diagnosis, a definitive histologic diagnosis, or both diagnoses as well as diagnostic ultrasound (US) examinations were available. All nodules were categorized using the ACR TI-RADS, and they were divided into three groups according to the recommendation received: fine-needle aspiration (group 1), follow-up US examination (group 2), or no further evaluation (group 3). RESULTS. Of the 3422 nodules, 352 were malignant. Of these, 240 nodules were assigned to group 1, whereas 72 were assigned to group 2 and 40 were included in group 3. Sixteen of the 40 malignant nodules in group 3 were 1 cm or larger, and, on the basis of analysis of the sonographic features described in the ACR TI-RADS, these nodules were classified as having one of five ACR TI-RADS risk levels (TR1-TR5), with one nodule classified as a TR1 nodule, eight as TR2 nodules, and seven as TR3 nodules. If the current recommendation of no follow-up for TR2 nodules was changed to follow-up for nodules 2.5 cm or larger, seven additional malignant nodules and 316 additional benign nodules would receive a recommendation for follow-up. If the current size threshold (1.5 cm) used to recommend US follow-up for TR3 nodules was decreased to 1.0 cm, seven additional malignant nodules and 118 additional benign nodules would receive a recommendation for follow-up. CONCLUSION. With use of the ACR TI-RADS, most malignant nodules that would not be biopsied would undergo US follow-up, would be smaller than 1 cm, or would both undergo US follow-up and be smaller than 1 cm. Adjusting size thresholds to decrease the number of missed malignant nodules that are 1 cm or larger would result in a substantial increase in the number of benign nodules undergoing follow-up.

Update on ACR TI-RADS: Successes, Challenges, and Future Directions, From the AJR Special Series on Radiology Reporting and Data Systems.

The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) is an ultrasound-based risk stratification system (RSS) for thyroid nodules that was released in 2017. Since publication, research has shown that ACR TI-RADS has a higher specificity than other RSSs and reduces the number of unnecessary biopsies of benign nodules compared with other systems by 19.9-46.5%. The risk of missing significant cancers using ACR TI-RADS is mitigated by the follow-up recommendations for nodules that do not meet criteria for biopsy. In practice, after a nodule's ultrasound features have been enumerated, the ACR TI-RADS points-based approach leads to clear management recommendations. Practices seeking to implement ACR TI-RADS must engage their radiologists in understanding how the system addresses the problems of thyroid cancer overdiagnosis and unnecessary surgeries by reducing unnecessary biopsies. This review compares ACR TI-RADS to other RSSs and explores key clinical questions faced by practices considering its implementation. We also address the challenge of reducing interobserver variability in assigning ultrasound features. Finally, we highlight emerging imaging techniques and recognize the ongoing international effort to develop a system that harmonizes multiple RSSs, including ACR TI-RADS.

Using the American College of Radiology Thyroid Imaging Reporting and Data System at the Point of Care: Sonographer Performance and Interobserver Variability.

The purpose of this study was to assess inter-observer variability and performance when sonographers assign features to thyroid nodules on ultrasound using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Fifteen sonographers retrospectively evaluated 100 thyroid nodules and assigned features to each nodule according to ACR TI-RADS lexicon. Ratings were compared with one another and to a gold standard using Fleiss' and Cohen's kappa statistics, respectively. Sonographers were also asked subjective questions regarding their comfort level assessing each feature, and opinions were compared with performance using a mixed effects model. Sonographers demonstrated only slight agreement for margin (κ = 0.18, 95% confidence interval [CI]: 0.16-0.20) and large comet tail artifact (κ = 0.08, 95% CI: 0.06-0.10) but better performance for macrocalcification (κ = 0.41, 95% CI: 0.39-0.43) and no echogenic foci (κ = 0.52, 95% CI: 0.50-0.54). Sonographer comfort level with different feature assignments did not statistically correlate with performance for a given feature. In conclusion, sonographers using ACR TI-RADS to assign thyroid nodule features on ultrasound demonstrate a range of agreement across features, with margin and large comet tail artifact showing the most variability. These results highlight potential areas of focus for sonographer education efforts as ACR TI-RADS continues to be implemented in radiology departments.

Deep Learning-Based Segmentation of Nodules in Thyroid Ultrasound: Improving Performance by Utilizing Markers Present in the Images.

Computer-aided segmentation of thyroid nodules in ultrasound imaging could assist in their accurate characterization. In this study, using data for 1278 nodules, we proposed and evaluated two methods for deep learning-based segmentation of thyroid nodules that utilize calipers present in the images. The first method used approximate nodule masks generated based on the calipers. The second method combined manual annotations with automatic guidance by the calipers. When only approximate nodule masks were used for training, the achieved Dice similarity coefficient (DSC) was 85.1%. The performance of a network trained using manual annotations was DSC = 90.4%. When the guidance by the calipers was added, the performance increased to DSC = 93.1%. An increase in the number of cases used for training resulted in increased performance for all methods. The proposed method utilizing the guidance by calipers matched the performance of the network that did not use it with a reduced number of manually annotated training cases.