Use of Predictive Modeling to Tailor Molecular Testing Utilization for Thyroid Nodules

2021 ◽  
pp. 019459982110041
Author(s):  
Sadia T. Ahmed ◽  
Stevyn Fernandes ◽  
Qi Gao ◽  
Thomas J. Ow ◽  
Richard V. Smith ◽  
...  

Objective Various risk stratification systems for cytologically indeterminate thyroid nodules are available. However, malignancy risk assessment data, such as ultrasound features, are not always used when the decision is to order molecular testing or not. Our aim was to investigate the utility of molecular testing after incorporating an algorithm with ultrasound-based risk of malignancy (ROM) estimation. Study Design Diagnostic/prognostic study. Setting Single-institution urban tertiary care center. Methods We performed a single-institution retrospective chart review of all thyroid nodules that had undergone molecular testing. A web-based Malignancy Risk Estimation System for Thyroid Nodules was utilized with ultrasound findings to stratify malignancy risk according to the Korean Thyroid Imaging Reporting and Data System (TI-RADS), French TI-RADS, American Association of Clinical Endocrinology guideline, and American Thyroid Association guideline. A novel algorithm for utilizing molecular testing at our institution was developed with the Korean TI-RADS and with recommendations from the American Thyroid Association and National Comprehensive Cancer Network. Results The Korean TI-RADS performed best in our population (area under the curve = 0.83). A positive molecular test result had a positive association with a higher ROM according to all 4 models ( P < .05). Use of our algorithm prior to molecular testing would have prevented 38% of benign/low-ROM negative nodules (n = 28) from being tested. Conclusion In patients with indeterminate thyroid nodules, an algorithm built on pre- and posttest probability to guide molecular testing might reduce unnecessary testing of benign and low-risk nodules.

2020 ◽  
Vol 26 (8) ◽  
pp. 857-868 ◽  
Author(s):  
Natalia Genere ◽  
Maria Daniela Hurtado ◽  
Tiffany Cortes ◽  
Shobana Athimulam ◽  
Ruaa Al Ward ◽  
...  

Objective: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center. Methods: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied. Results: We identified 141 nodules in 129 patients: mean age 58.1 ± 14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5–188.7]), radiology recommendation for biopsy (OR 2.6 [1.8–3.9]) and radiology report of the nodule as “suspicious” (OR 2.1 [1.4–3.2]). Patient’s age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations. Conclusion: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules. Abbreviations: ATA = American Thyroid Association; OR = odds ratio


2020 ◽  
Vol 103 (11) ◽  
pp. 1220-1229

Objective: To describe clinical characteristics and outcomes of laboratory-confirmed influenza in hospitalized children in a tertiary care center and to identify factors associated with the severity. Materials and Methods: The present study was a retrospective medical chart review study conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Data were extracted from children aged under 15 years old hospitalized between January 2014 and December 2018. Patients who had laboratory-confirmed influenza by rapid antigen detection or molecular testing were included. Severe influenza was defined as patients who developed influenza complications or duration of hospitalization for more than three days. Multivariate logistic regression was used to identify the associated factors with the severity of the disease. Results: Three hundred fifty-seven influenza patients were included with median age of 43 months (IQR 19 to 81), of which 63.3% were aged under 60 months. There were 174 patients (48.7%) with comorbidities, most common were immunosuppression (18.2%), chronic pulmonary disease (12.2%), and congenital heart disease (11.5%). Fifty-seven out of 183 patients (31.1%) had history of influenza vaccination in the medical records. One hundred sixty-one patients (45.1%) had 212 influenza complications including influenza-related pneumonia (89, 24.9%), secondary bacterial infection (53, 14.8%), and neurologic complications (47, 13.2%), in which 27 cases (7.6%) were transferred to intensive care unit (ICU). Four cases (1.1%) died but not directly related to influenza. Associated factors with complicated influenza were aged less than 24 months [aOR 2.67 (95% CI 1.68 to 4.26)] and presence of chronic lung disease [aOR 4.34 [95% CI 2.01 to 9.35)]. Conclusion: Two-third of the children hospitalized with influenza were younger than 60 months. Nearly half developed complications most associated with the age of less than two years old and patients with chronic lung disease. Low rates of vaccination were demonstrated. Keywords: Influenza, Pediatrics, Complications, Pneumonia, Hospitalization


2021 ◽  
Vol 27 ◽  
pp. 107602962110228
Author(s):  
Bushra Moiz ◽  
Ronika Devi Ukrani ◽  
Aiman Arif ◽  
Inaara Akbar ◽  
Muhammed Wahhaab Sadiq ◽  
...  

Pediatric cerebral venous sinus thrombosis (CVST) is rare but a potentially fatal disease requiring its understanding in local setting. In this study, we observed the clinical course, management, and outcome of pediatric patients with sinus thrombosis in a tertiary care center at Pakistan. Patients between age 0 to 18 years of both genders diagnosed with sinus thrombosis during 2011 to 2020 were included. Data was collected through in-house computerized system and SPSS version 19 was used for analysis. Of 143492 pediatric admissions, 32 (21 males and 11 females) patients with a median (IQR) age of 4.5 years (0-16) had CVST. This is equivalent to 18.5 CVST events per million pediatric admissions. Adolescents were mostly affected, and the overall mortality was 7%. Primary underlying disorders were infections (59%), hematological neoplasms (12.5%), thrombotic thrombocytopenic purpura (3%) and antiphospholipid syndrome (3%). Activated protein C resistance (44%) was the most common inherited thrombophilia. Twenty-one (66%) patients were anemic with a mean (±SD) hemoglobin of 9.0 g/dL (±2.3). Regression analysis showed a positive association of anemia with multiple sinus involvement ( P-value 0.009) but not with duration of symptoms ( P-value 0.344), hospital stay ( P-value 0.466), age ( P-value 0.863) or gender ( P-value 0.542) of the patients. SARS-COV2 was negative in patients during 2020. Adolescents were primarily affected by sinus thrombosis and infections was the predominant risk factor for all age groups, with a low all-cause mortality. A high index of clinical suspicion is required for prompt diagnosis and intervention.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Thayse Lozovoy Madsen Barbosa ◽  
Cleo Otaviano Mesa Junior ◽  
Hans Graf ◽  
Teresa Cavalvanti ◽  
Marcus Adriano Trippia ◽  
...  

Abstract Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p < 0.001) among Bethesda III, IV and V was observed. The rate of malignancy increased according to the US suspicion categories (p < 0.001) in both US classifications (TI-RADS and ATA). Thyroid nodules classified as Bethesda III and the lowest risk US categories (very low, low and intermediate suspicion by ATA and 2, 3 and 4a by TI-RADS) displayed a sensitivity of 95.3% for both classifications and a negative predictive value of 94.3 and 94.1%, respectively. The highest risk US categories (high suspicion by ATA and 4b,4c and 5 by TI-RADS) were significantly associated with cancer (odds ratios [ORs] 14.7 and 9.8, respectively). Conclusions Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.


2021 ◽  
Vol 8 ◽  
Author(s):  
Shan Jiang ◽  
Qingji Xie ◽  
Nan Li ◽  
Haizhen Chen ◽  
Xi Chen

To assess the malignancy risk of thyroid nodules, ten ultrasound characteristics are suggested as key diagnostic markers. The European Thyroid Association Guidelines (EU-TIRADS) and 2015 American Thyroid Association Management Guidelines (2015ATA) are mainly used for ultrasound malignancy risk stratification, but both are less accurate and do not appropriatetly classify high risk patients in clinical examination. Previous studies focus on papillary thyroid carcinoma (PTC), but follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC) remained to be characterized. Thus, this study aimed to determine the diagnostic accuracy and establish models using all ultrasound features including the nodule size for predicting the malignancy of thyroid nodules (PTC, FTC, and MTC) in China. We applied logistic regression to the data of 1,500 patients who received medical treatment in Shanghai and Fujian. Ultrasound features including taller-than-wide shape and invasion of the thyroid capsule showed high odds ratio (OR 19.329 and 4.672) for PTC in this dataset. Invasion of the thyroid also showed the highest odds ratio (OR = 8.10) for MTC. For FTC, the halo sign has the highest odds ratio (OR = 13.40). Four ultrasound features revealed distinct OR in PTC nodule groups with different sizes. In this study, we constructed a logistic model with accuracy up to 80%. In addition, this model revealed more accuracy than TIRADS in 4b and 4c category nodules. Hence, this model could well predict malignancy in small nodules and classify high-risk patients.


2020 ◽  
Vol 6 (5) ◽  
pp. e273-e278
Author(s):  
Ruey Hu ◽  
George Xu ◽  
Thomas Stricker ◽  
Bingshan Li ◽  
Vivian L. Weiss ◽  
...  

Objective: Here we present 2 cases of papillary thyroid microcarcinomas (PMCs) that had metastasized at presentation. The 2015 American Thyroid Association and the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) criteria do not recommend biopsy of the majority of subcentimeter thyroid nodules, as PMCs are mostly indolent with excellent prognosis. However, the paradigm of active surveillance presents a conundrum on how to identify the rare patient with distant metastatic disease while avoiding unnecessary intervention in the majority. Methods: After initial discovery of incidental lesions on chest computed tomography, core or wedge biopsies of the lung lesion were performed. Thyroid nodules on ultrasound were classified by TI-RADS. Tumor DNA was sequenced, annotated, filtered on 119 known cancer genes, and filtered for variants with an exome allele frequency of <0.001. Results: A 70-year-old woman and a 29-year-old woman presented with incidental pulmonary lesions on computed tomography scan. Lung biopsy revealed lung metastases from papillary thyroid carcinoma. The thyroid nodules in both patients were TI-RADS 3 and American Thyroid Association low-suspicion. Molecular testing showed a c.1721C>G mutation (p.Thr574Ser) in the TSHR gene in patient 1 and a codon 61 mutation in the NRAS gene in patient 2. Both patients were iodine-avid, with complete structural remission in one patient and ongoing treatment with evidence of structural response in the other. Conclusion: The 2 presentations demonstrate unexpected and concerning behavior of PMCs. Both thyroid tumors were subcentimeter in diameter, meaning they would have escaped detection using traditional risk-stratification algorithms in active surveillance. Further knowledge of tumor genetics and microenvironment may assist in predicting tumor behavior in PMCs.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 736 ◽  
Author(s):  
Esther Diana Rossi ◽  
Liron Pantanowitz ◽  
William C. Faquin

Thyroid nodules are common in the adult population where a majority are benign and only 4.0% to 6.5% are malignant. Fine needle aspiration (FNA) is a key method used in the early stages to evaluate and triage patients with thyroid nodules. While a definitive cytological diagnosis is provided in more than 70–75% of all thyroid FNA cases, the group of indeterminate lesions offers a challenge in terms of interpretation and clinical management. Molecular testing platforms have been developed, are recognized as an option by the 2015 American Thyroid Association Guidelines, and are frequently used in conjunction with FNA as an integral part of the cytologic evaluation. In this review, the utility of molecular testing options for nodules assigned to the group of indeterminate thyroid FNAs is described.


Author(s):  
Kalpesh Hathi ◽  
Tarek Rahmeh ◽  
Vicki Munro ◽  
Victoria Northrup ◽  
Ali Sherazi ◽  
...  

Abstract Background Thyroid nodules are stratified through fine-needle aspiration (FNA) and are often categorized using The Bethesda System for Reporting Thyroid Cytopathology, which estimates the risk of malignancy for six cytopathological categories. The atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) categories have varying malignancy rates reported in the literature which can range from 6 to 72.9%. Due to this heterogeneity, we assessed the malignancy rate and effectiveness of repeat FNA (rFNA) for AUS/FLUS thyroid cytopathology at our institution. Methods Electronic health records of patients with AUS/FLUS thyroid cytopathology on FNA at our center since the implementation of the Bethesda System on May 1, 2014–December 31, 2019 were retrospectively reviewed. Patient demographics, treatment pathway, and pathology results were collected. The treatment pathway of the nodules, the rFNA results, and the malignant histopathology results were reported. Malignancy rates were calculated as an upper and lower limit estimate. Results This study described 182 AUS/FLUS thyroid nodules from 177 patients. In total, 24 thyroid nodules were deemed malignant upon histopathology, yielding a final malignancy rate of 13.2–25.3%. All of the malignancies were variants of papillary thyroid carcinoma. The malignancy rate of the nodules which underwent resection without rFNA (21.5%) was lower than the malignancy rate of the nodules which underwent resection after rFNA (43.8%). 45.5% of the rFNA results were re-classified into more definitive categories. Conclusion The malignancy rate of AUS/FLUS thyroid cytopathology at our center is in line with the risk of malignancy stated by the 2017 Bethesda System. However, our malignancy rate is lower than some other Canadian centers and approximately half of our rFNAs were re-classified, highlighting the importance of establishing center-specific malignancy and rFNA re-classification rates to guide treatment decisions.


Author(s):  
Claire L. Wittowski ◽  
Sarah Clowes Candadai ◽  
Marie E. Perrone ◽  
Daniel F. Gallego ◽  
Jessie H. Conta ◽  
...  

Context.— Genomic molecular testing practices in a pediatric tertiary care institution. Objective.— To evaluate exome sequencing (ES) ordering practices and the effects of applying criteria to support ES stewardship. Exome sequencing can provide molecular diagnostic information for patients with known or suspected genetic diseases, but it is relatively expensive, and the cost is often borne by patients, institutions, and payers. Design.— We examined ordering patterns of ES approved by board-certified geneticists at our tertiary pediatric care center, as well as preauthorization outcomes for ES requests. We compared positivity rates among patients by patient phenotype, composite insurance coverage criteria, and insurance preauthorization outcome. Results.— Patients who met composite coverage criteria were more likely to receive a positive result from ES compared to patients who did not meet composite coverage criteria, though this trend was not statistically significant. There was no significant difference in ES results between patients who were denied or not denied preauthorization by insurance payers. Conclusions.— Insurance payers should consider implementing and/or expanding coverage criteria for ES and institutions should implement stewardship programs to support appropriate ES practices.


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