Evaluating Patients' Health Literacy to Improve Thyroid Pathology Reports.

INTRODUCTION: As our growing population demonstrates a significant increase in the incidence of thyroid cancer, so does patient access to their medical records. Poor health literacy and understanding of disease severity, underscores the importance of effective and accessible patient-doctor communication. No previous studies on patient understanding of thyroid pathology reports exist; therefore, we sought to characterize health literacy in this population. METHODS: Using a modified Delphi technique, a 12-question multiple-choice survey regarding common pathology terms with possible definitions for each term was synthesized and administered to patients in a high-volume endocrine surgery clinic. Survey results, patient demographics, history of prior thyroid procedure (biopsy or surgery), and self-reported health literacy were collected. Data analysis included t tests, chi-squared, and multivariable linear regression using R. RESULTS: The survey was completed by 54 patients (response rate: 69.8%). On univariate analysis, White race, previous thyroid procedure, and at least a high school level education were all more likely to score higher on the survey than their counterparts (P < 0.05). On multivariable logistic regression for predicting a higher survey score, only race (est: 2.48 [95% confidence interval: 1.01-3.96]) and higher educational attainment (est: 3.98 [95% confidence interval: 2.32-5.64]) remained predictive (P < 0.05). The remaining demographic groups (age, health literacy confidence, and previous thyroid procedure) did not show a statistically significant difference. CONCLUSIONS: Overall, terms on a thyroid pathology report are poorly understood by patients. This is exacerbated by non-White race and low educational attainment. There is a need for patient-facing pathology education.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.

BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment.

Somatostatin receptor type 2 (SSTR2) and thyroid-stimulating hormone receptor (TSHR) display variable expression in primary thyroid tumors and have been implicated as theranostic targets. This study was designed to explore the differential expression of SSTR2 and TSHR in oncocytic (Hurthle cell) carcinoma (OC) vs oncocytic adenoma (OA). We performed a retrospective review for oncocytic neoplasms treated at our institution from 2012 to 2019. Formalin-fixed paraffin-embedded tissue blocks were used for tissue microarray construction. Tissue microarray blocks were cut into 5-µm sections and stained with anti-SSTR2 and anti-TSHR antibodies. Immunostains were analyzed by 3 independent pathologists. χ2 and logistic regression analysis were used to analyze clinical and pathologic variables. Sixty-seven specimens were analyzed with 15 OA and 52 OC. The mean age was 57 years, 61.2% were women, and 70% were White. SSTR2 positivity was noted in 2 OA (13%) and 15 OC (28%; 10 primary, 4 recurrent, and 1 metastatic) (P = .22). TSHR positivity was noted in 11 OA (73%) and 32 OC (62%; 31 primary and 1 metastatic) (P = .40). Those who presented with or developed clinical recurrence/metastasis were more likely to be SSTR2-positive (50% vs 21%; P = .04) and TSHR-negative (64.3% vs 28.9%; P = .02) than primary OC patients. Widely invasive OC was more likely to be SSTR2-positive compared to all other OC subtypes (minimally invasive and angioinvasive) (P = .003). For all patients with OC, TSHR positivity was inversely correlated with SSTR2 positivity (odds ratio, 0.12; CI, 0.03-0.43; P = .006). This relationship was not seen in the patients with OA (odds ratio, 0.30; CI, 0.01-9.14; P = .440). Our results show that recurrent/metastatic OC was more likely to be SSTR2-positive and TSHR-negative than primary OC. Patients with OC displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in patients with OA. This may be a key relationship that can be used to prognosticate and treat OCs.

Determining The Role Of Radiation Oncologist Demographic Factors On Segmentation Quality: Insights From A Crowd-Sourced Challenge Using Bayesian Estimation.

BACKGROUND: Medical image auto-segmentation is poised to revolutionize radiotherapy workflows. The quality of auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of these clinician-derived segmentations have yet to be fully understood or quantified. Therefore, the purpose of this study was to determine the role of common observer demographic variables on quantitative segmentation performance. METHODS: Organ at risk (OAR) and tumor volume segmentations provided by radiation oncologist observers from the Contouring Collaborative for Consensus in Radiation Oncology public dataset were utilized for this study. Segmentations were derived from five separate disease sites comprised of one patient case each: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and gastrointestinal (GI). Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus gold standard primarily using the Dice Similarity Coefficient (DSC); surface DSC was investigated as a secondary metric. Metrics were stratified into binary groups based on previously established structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Markov chain Monte Carlo Bayesian estimation were used to investigate the association between demographic variables and the binarized segmentation quality for each disease site separately. Variables with a highest density interval excluding zero - loosely analogous to frequentist significance - were considered to substantially impact the outcome measure. RESULTS: After filtering by practicing radiation oncologists, 574, 110, 452, 112, and 48 structure observations remained for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of observations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumor volumes, respectively. Bayesian regression analysis revealed tumor category had a substantial negative impact on binarized DSC for the breast (coefficient mean ± standard deviation: -0.97 ± 0.20), sarcoma (-1.04 ± 0.54), H&N (-1.00 ± 0.24), and GI (-2.95 ± 0.98) cases. There were no clear recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations and wide highest density intervals. CONCLUSION: Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality. Future studies should investigate additional demographic variables, more patients and imaging modalities, and alternative metrics of segmentation acceptability.

Pharmaceuticals, pesticides, and ultraviolet filters in wastewater discharges to San Francisco Bay as drivers of ecotoxicity.

Research in the United States evaluating ecotoxic risk to receiving waters posed by contaminants occurring in wastewater discharges typically has focused on measurements of pharmaceuticals and personal care products (PPCPs), with limited evaluations of UV filters and phenylpyrazole and neonicotinoid pesticides. In this study, concentrations of 5 representative pharmaceuticals, 11 pesticides or pesticide degradation products, and 5 ultraviolet filters were measured in 24 h composite samples of six wastewater discharges representing ∼70% of the total wastewater discharged to San Francisco Bay during the summer and fall of 2021. No significant difference was observed between concentrations measured on weekdays vs. weekends. A hydrodynamic model of San Francisco Bay was used to estimate annual average dilution factors associated with different subembayments. With and without considering dilution effects, Risk Quotients were calculated using the 90th percentile of measured concentrations in wastewater effluents and threshold concentrations associated with ecotoxicity. Risk Quotients were highest for the neonicotinoid pesticide, imidacloprid, and exceeded ecotoxicity thresholds in the lower South Bay by a factor of 2.4, even when considering dilution. Compared to commonly measured pharmaceuticals, Risk Quotients for imidacloprid were higher than those for carbamazepine, trimethoprim and diclofenac, and comparable to those for propranolol and metoprolol. Risk Quotients for the pesticide, fipronil, and the UV filter, oxybenzone, were higher than for carbamazepine. The results highlight the need to incorporate pesticides and UV filters with high Risk Quotients into studies in the United States evaluating ecotoxic risk associated with contaminants in municipal wastewater discharges.

Faulty Metabolism: A Potential Instigator of an Aggressive Phenotype in Cdk5-dependent Medullary Thyroid Carcinoma.

Mechanistic modeling of cancers such as Medullary Thyroid Carcinoma (MTC) to emulate patient-specific phenotypes is challenging. The discovery of potential diagnostic markers and druggable targets in MTC urgently requires clinically relevant animal models. Here we established orthotopic mouse models of MTC driven by aberrantly active Cdk5 using cell-specific promoters. Each of the two models elicits distinct growth differences that recapitulate the less or more aggressive forms of human tumors. The comparative mutational and transcriptomic landscape of tumors revealed significant alterations in mitotic cell cycle processes coupled with the slow-growing tumor phenotype. Conversely, perturbation in metabolic pathways emerged as critical for aggressive tumor growth. Moreover, an overlapping mutational profile was identified between mouse and human tumors. Gene prioritization revealed putative downstream effectors of Cdk5 which may contribute to the slow and aggressive growth in the mouse MTC models. In addition, Cdk5/p25 phosphorylation sites identified as biomarkers for Cdk5-driven neuroendocrine tumors (NETs) were detected in both slow and rapid onset models and were also histologically present in human MTC. Thus, this study directly relates mouse and human MTC models and uncovers vulnerable pathways potentially responsible for differential tumor growth rates. Functional validation of our findings may lead to better prediction of patient-specific personalized combinational therapies.

PD-L1 (22C3) Expression Correlates with Clinical and Molecular Features of Lung Adenocarcinomas in Cytological Samples.

INTRODUCTION: PD-L1 expression is the most widely used predictive marker for immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. However, the current understanding of the association between PD-L1 expression and treatment response is suboptimal. A significant percentage of patients have only a cytological specimen available for clinical management. Therefore, it is relevant to examine the impact of molecular features on PD-L1 expression in cytological samples and how it might correlate with a therapeutic response. METHODS: We evaluated patients diagnosed with adenocarcinoma of the lung who had both in-house targeted next-generation sequencing analysis and paired PD-L1 (22C3) immunohistochemical staining performed on the same cell blocks. We explored the association between molecular features and PD-L1 expression. In patients who underwent ICIs therapy, we assessed how a specific gene mutation impacted a therapeutic response. RESULTS: 145 patients with lung adenocarcinoma were included in this study. PD-L1-high expression was found to be more common in pleural fluid than in other sample sites. Regional lymph node samples showed a higher proportion of PD-L1-high expression (29%) compared with lung samples (6%). The predictive value of PD-L1 expression was retained in cytological samples. Mutations in KRAS were also associated with a PD-L1-high expression. However, tumors with TP53 or KRAS mutations showed a lower therapy response rate regardless of the PD-L1 expression. CONCLUSION: Cytological samples maintain a predictive value for PD-L1 expression in patients with lung adenocarcinoma as regards the benefit of ICI treatment. Specific molecular alterations additionally impact PD-L1 expression and its predictive value.

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells.

Our results from quantitative RT-PCR, Western blotting, immunohistochemistry, and the tissue microarray of medullary thyroid cancer (MTC) cell lines and patient specimens confirm that VGSC subtype NaV1.7 is uniquely expressed in aggressive MTC and not expressed in normal thyroid cells and tissues. We establish the druggability of NaV1.7 in MTC by identifying a novel inhibitor (SV188) and investigate its mode of binding and ability to inhibit INa current in NaV1.7. The whole-cell patch-clamp studies of the SV188 in the NaV1.7 channels expressed in HEK-293 cells show that SV188 inhibited the INa current in NaV1.7 with an IC50 value of 3.6 µM by a voltage- and use-dependent blockade mechanism, and the maximum inhibitory effect is observed when the channel is open. SV188 inhibited the viability of MTC cell lines, MZ-CRC-1 and TT, with IC50 values of 8.47 µM and 9.32 µM, respectively, and significantly inhibited the invasion of MZ-CRC-1 cells by 35% and 52% at 3 µM and 6 µM, respectively. In contrast, SV188 had no effect on the invasion of TT cells derived from primary tumor, which have lower basal expression of NaV1.7. In addition, SV188 at 3 µM significantly inhibited the migration of MZ-CRC-1 and TT cells by 27% and 57%, respectively.

Large scale crowdsourced radiotherapy segmentations across a variety of cancer anatomic sites.

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches. However, extant segmentation datasets typically only provide segmentations generated by a limited number of annotators with varying, and often unspecified, levels of expertise. In this data descriptor, numerous clinician annotators manually generated segmentations for ROIs on computed tomography images across a variety of cancer sites (breast, sarcoma, head and neck, gynecologic, gastrointestinal; one patient per cancer site) for the Contouring Collaborative for Consensus in Radiation Oncology challenge. In total, over 200 annotators (experts and non-experts) contributed using a standardized annotation platform (ProKnow). Subsequently, we converted Digital Imaging and Communications in Medicine data into Neuroimaging Informatics Technology Initiative format with standardized nomenclature for ease of use. In addition, we generated consensus segmentations for experts and non-experts using the Simultaneous Truth and Performance Level Estimation method. These standardized, structured, and easily accessible data are a valuable resource for systematically studying variability in segmentation applications.

E pluribus unum: prospective acceptability benchmarking from the Contouring Collaborative for Consensus in Radiation Oncology crowdsourced initiative for multiobserver segmentation.

Purpose: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement. Approach: Participants who contoured ≥ 1 region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) cases were identified as a nonexpert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. STAPLE nonexpert ROIs were evaluated against STAPLE expert contours using Dice similarity coefficient (DSC). The expert interobserver DSC ( IODSC expert ) was calculated as an acceptability threshold between STAPLE nonexpert and STAPLE expert . To determine the number of nonexperts required to match the IODSC expert for each ROI, a single consensus contour was generated using variable numbers of nonexperts and then compared to the IODSC expert . Results: For all cases, the DSC values for STAPLE nonexpert versus STAPLE expert were higher than comparator expert IODSC expert for most ROIs. The minimum number of nonexpert segmentations needed for a consensus ROI to achieve IODSC expert acceptability criteria ranged between 2 and 4 for breast, 3 and 5 for sarcoma, 3 and 5 for H&N, 3 and 5 for GYN, and 3 for GI. Conclusions: Multiple nonexpert-generated consensus ROIs met or exceeded expert-derived acceptability thresholds. Five nonexperts could potentially generate consensus segmentations for most ROIs with performance approximating experts, suggesting nonexpert segmentations as feasible cost-effective AI inputs.

Histology segmentation using active learning on regions of interest in oral cavity squamous cell carcinoma.

In digital pathology, deep learning has been shown to have a wide range of applications, from cancer grading to segmenting structures like glomeruli. One of the main hurdles for digital pathology to be truly effective is the size of the dataset needed for generalization to address the spectrum of possible morphologies. Small datasets limit classifiers' ability to generalize. Yet, when we move to larger datasets of whole slide images (WSIs) of tissue, these datasets may cause network bottlenecks as each WSI at its original magnification can be upwards of 100 000 by 100 000 pixels, and over a gigabyte in file size. Compounding this problem, high quality pathologist annotations are difficult to obtain, as the volume of necessary annotations to create a classifier that can generalize would be extremely costly in terms of pathologist-hours. In this work, we use Active Learning (AL), a process for iterative interactive training, to create a modified U-net classifier on the region of interest (ROI) scale. We then compare this to Random Learning (RL), where images for addition to the dataset for retraining are randomly selected. Our hypothesis is that AL shows benefits for generating segmentation results versus randomly selecting images to annotate. We show that after 3 iterations, that AL, with an average Dice coefficient of 0.461, outperforms RL, with an average Dice Coefficient of 0.375, by 0.086.

Radiation Oncology AcaDemic Mentorship Program (ROADMAP) for Junior Faculty: One-Year Results of a Prospective Single Institution Initiative.

PURPOSE: Although mentorship has been associated with promotion, job satisfaction, and retention, data are limited on the mentorship experience of clinical- versus research-track physicians as well as feasibility and relative priority of formal program components. METHODS AND MATERIALS: Within a single-institution, multi-site, academic network, we implemented a Radiation Oncology AcaDemic Mentorship Program (ROADMAP) for junior faculty. Validated surveys assessing mentee satisfaction were distributed at baseline and 1 year. The statistical analysis included Wilcoxon rank sum and signed tests. Mentees assessed the likelihood to recommend each program component (10-point Likert-type scale), and means with standard error (SE) are reported. RESULTS: Among 42 eligible junior faculty, 36 (86%) opted into the program. The median time since residency was 2.5 years (interquartile range, 1.75-5.25) on the clinical track (n = 12) and 3 years (interquartile range, 2.75-5.00) on the research track (n = 24). At baseline, research-track physicians reported higher satisfaction with mentoring than physicians on the clinical track (2.92 vs 2.16; P = .02). Among 32 physicians completing 1 year, overall satisfaction with mentoring increased compared with baseline (2.72 vs 3.87; P < .001), which persisted on subset analysis for both clinical- (2.16 vs 4.03; P < .001) and research-track physicians (2.99 vs 3.77; P = .005). At 1 year, 28 mentees (88%) opted to continue the program. Program components were rated 8.25 (SE, 0.37) for mentor-mentee pairings, 7.22 (SE, 0.39) for goal setting, 6.84 (SE, 0.47) for administrative support, 6.69 (SE, 0.44) for peer mentoring, and 6.53 (SE, 0.45) for steering committee oversight. Ratings of peer mentoring were not associated with track (P = .59) or years in practice (P = .29). CONCLUSIONS: Clinical-track physicians may be less satisfied with mentorship than research-track faculty. However, all junior faculty, regardless of track, appeared to benefit from formalizing dyadic mentor-mentee relationships, goal setting, and peer mentoring. Further work is needed to determine the role of mentorship in addressing physician burnout.

Multidisciplinary Treatment of Non-Spine Bone Metastases: Results of a Modified Delphi Consensus Process.

Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.

Implementation Strategies to Increase Clinical Trial Enrollment in a Community-Academic Partnership and Impact on Hispanic Representation: An Interrupted Time Series Analysis.

PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

Incidental Thyroid Nodules Found During Acute Stroke Angiography: Prevalence, Outcomes, and Suggested Management Guidelines.

OBJECTIVE: In stroke patients, extensive interventions for incidental thyroid nodules can be burdensome and costly. It appears that the risk of malignancy has not been reported in angiographically detected nodules and outcomes have not yet been described in patients, receiving acute stroke work-up. MATERIALS AND METHODS: Incidental thyroid nodules were found on neck computerized tomography angiography or magnetic resonance angiography performed during inpatient stroke workup (January 2017 to September 2019). These patient cases were reviewed based on sonography reports, diagnosis, and follow-up care. RESULTS: Of the 13 563 patients, 192 had incidental thyroid nodules (prevalence 1.4%). Twenty-six died from comorbidities and 22 received thyroid sonography. Twelve nodules from 10 patients had sonographic characteristics for biopsy: 10 benign, 1 indeterminate, and 1 papillary thyroid cancer (risk of malignancy: 8%). The cancer patient underwent hemithyroidectomy and is disease-free. Follow-up of the remaining patients showed no worsening or suspicious nodules. The American College of Radiology (ACR) guidelines would have prevented 8 unnecessary sonograms and 1 biopsy without missing malignancy. CONCLUSION: Although a small risk of malignancy was noted, 95% of patients undergoing additional diagnostic thyroid testing had clinically insignificant results. The ACR guidelines can prevent unnecessary interventions. Given the 14% mortality rate in the study cohort, it is proposed that a clinical evaluation of patients is important before undergoing further diagnostics, as comorbidities may be worse than a thyroid cancer.

Metrics to evaluate the performance of auto-segmentation for radiation treatment planning: A critical review.

Advances in artificial intelligence-based methods have led to the development and publication of numerous systems for auto-segmentation in radiotherapy. These systems have the potential to decrease contour variability, which has been associated with poor clinical outcomes and increased efficiency in the treatment planning workflow. However, there are no uniform standards for evaluating auto-segmentation platforms to assess their efficacy at meeting these goals. Here, we review the most frequently used evaluation techniques which include geometric overlap, dosimetric parameters, time spent contouring, and clinical rating scales. These data suggest that many of the most commonly used geometric indices, such as the Dice Similarity Coefficient, are not well correlated with clinically meaningful endpoints. As such, a multi-domain evaluation, including composite geometric and/or dosimetric metrics with physician-reported assessment, is necessary to gauge the clinical readiness of auto-segmentation for radiation treatment planning.

Is Regional Lymph Node Metastasis of Head and Neck Paraganglioma a Sign of Aggressive Clinical Behavior: A Clinical/Pathologic Review.

BACKGROUND: Head and neck paraganglioma is a rare neoplasm of the paraganglia. It accounts for <1% of all head and neck tumors. It usually has benign clinical course; however, malignant paraganglioma can only be diagnosed by showing metastatic disease. We undertook a retrospective study to assess the clinical significance of regional lymph nodes metastases in head and neck paragangliomas. DESIGN: From 1993 to 2016, primary head and neck paragangliomas are identified. The patient clinical and histopathologic materials were reviewed. RESULTS: Sixty-five specimens from 62 patients (3 patients with more than 1 specimens) with head and neck paragangliomas were recorded (49 female and 13 males) with mean age of 54 (24-78 years). The locations of the tumors were as follows: carotid body: 30, glomus tympanicum: 11, glomus jugulare: 14, parapharyngeal space: 3, and 1 case each of larynx, skull base, paraglottic area, infratemporal fossa, mastoid, cerebellopontine (CP) angle, and pyriform sinus. On histopathology, we found 5 cases of sclerosing variant. Thirty-two (52%) of the 62 patients had regional lymph node biopsy. Four (12%) of the 32 show metastatic paraganglioma (3 females and 1 male with mean age = 35). Two of the 5 cases of sclerosing variant had positive lymph nodes. No evidence of local recurrence or distant metastasis in the patients with positive lymph nodes with a 6 to 11 years follow-up. One of the 28 patients with negative lymph nodes developed metastatic disease to lumbar spine in 5 years. CONCLUSION: Metastatic paraganglioma to regional lymph nodes may have indolent clinical behavior, with disease-free survival of up to 11 years. The incidence of metastatic disease in lymph nodes was 4 (12%) of 32. Forty percent (2/5) of the cases with sclerosing variant of paraganglioma had lymph node metastases indicating that this tumor may have a more aggressive histological behavior.

Revisiting a rare disease: Oral cavity basaloid squamous cell carcinoma at a high-volume tertiary center.

OBJECTIVES: Rare diseases are often poorly understood, and this study sought to investigate the incidence of a rare disease entity, basaloid squamous cell carcinoma (BSCC) of the oral cavity (OC) at a tertiary care medical center and to assess its clinical outcomes. METHODS: The aim of this study was to collect data in order to better understand how this rare disease progresses. This was a case series of patients with OC BSCC diagnosed between 2001 and 2018. RESULTS: 10 patients with primary OC BSCC were identified. Average age at diagnosis was 58 years (33-71). The median follow-up period was 11 months. Primary sites included oral tongue (n = 4), floor of mouth (n = 4), hard palate (n = 1), and retromolar trigone (n = 1). A majority (60%) of patients had pathologic T3/T4 tumors. All patients underwent primary surgical treatment. There was an overall 60% mortality rate: 2 died from metastasis at 1- and 3-months postop, 2 from unknown causes, 1 from sepsis at 1 month postop, and 1 from metastatic colon cancer. Average survival for those patients who died was 20.7 months. 4 patients were disease-free at the time of publication. CONCLUSION: There are few studies in the literature that seek to investigate cases of OC BSCC from a single institution. This is the first detailed case series of BSCC from a single American institution. Survival outcomes in our cohort were poor but demonstrate a variable course of disease burden. This study presents unique information regarding specific pathologic characteristics and patient outcomes for this rare disease.

A Systematic Review of Contouring Guidelines in Radiation Oncology: Analysis of Frequency, Methodology, and Delivery of Consensus Recommendations.

PURPOSE: Clinical trials have described variation in radiation therapy plan quality, of which contour delineation is a key component, and linked this to inferior patient outcomes. In response, consensus guidelines have been developed to standardize contour delineation. This investigation assesses trends in contouring guidelines and examines the methodologies used to generate and deliver recommendations. METHODS AND MATERIALS: We conducted a literature search for contouring guidelines published after 1995. Of 11,124 citations, 332 were identified for full-text review to determine inclusion. We abstracted articles for the intent of the consensus process, key elements of the methodology, and mode of information delivery. A Fisher exact test was used to identify elements that differed among the guidelines generated for clinical trials and routine care. RESULTS: Overall, 142 guidelines were included, of which 16 (11%) were developed for a clinical trial. There was an increase in guideline publication over time (0 from 1995-1999 vs 65 from 2015- 2019; P = .03), particularly among recommendations for stereotactic radiation and brachytherapy. The most common disease sites were head and neck (24%), gastrointestinal (12%), and gynecologic (12%). Methods used to develop recommendations included literature review (50%) and image-based methods (45%). Panels included a median of 10 physicians (interquartile range, 7-16); 70% of panels represented multidisciplinary expertise. Guidelines developed for a clinical trial were more likely to include an image-based approach, with quantitative analysis of contours submitted by the panel members and to publish a full set of image-based recommendations (P < .005). CONCLUSIONS: This review highlights an increase in consensus contouring recommendations over time. Guidelines focus on disease sites, such as head and neck, with evidence supporting a correlation between treatment planning and patient outcomes, although variation exists in the approach to the consensus process. Elements that may improve guideline acceptance (ie, image-based consensus contour analysis) and usability (ie, inclusion of a full image set) are more common in guidelines developed for clinical trials.

Rapid On-Site Evaluation With Telecytology Significantly Reduced Unsatisfactory Rates of Thyroid Fine-Needle Aspiration.

OBJECTIVES: We evaluated telecytology rapid on-site evaluation (ROSE) for thyroid ultrasound-guided fine-needle aspiration. To the best of our knowledge, this study is the first case-control clinical trial of thyroid telecytology. METHODS: We introduced on-site ROSE in our institution's thyroid clinic for 6 months, followed by telecytology for 12 months. Our institution's ultrasound clinic, where ROSE is not provided, was used as a control group for each period. RESULTS: Both groups had similar initial unsatisfactory rates (thyroid clinic: 8.8%; ultrasound clinic: 8.0%) before the study began. The thyroid clinic's unsatisfactory rate was significantly reduced to 1.6% after on-site ROSE (P = .001) and to 3.8% after telecytology ROSE (P = .010), with no significant difference between on-site and telecytology ROSE periods (P > .05). The ultrasound clinic's unsatisfactory rate was unchanged for both periods. Concordance between telecytology ROSE and final adequacy was 97% (κ = 0.699). CONCLUSIONS: Telecytology ROSE reduces unsatisfactory rates for ultrasound-guided fine-needle aspiration without compromising patient care.