TY - JOUR
T1 - A Thyroid Genetic Classifier Correctly Predicts Benign Nodules with Indeterminate Cytology
T2 - Two Independent, Multicenter, Prospective Validation Trials
AU - Zafereo, Mark
AU - McIver, Bryan
AU - Vargas-Salas, Sergio
AU - Domínguez, José Miguel
AU - Steward, David L.
AU - Holsinger, F. Christopher
AU - Kandil, Emad
AU - Williams, Michelle
AU - Cruz, Francisco
AU - Loyola, Soledad
AU - Solar, Antonieta
AU - Roa, Juan Carlos
AU - León, Augusto
AU - Droppelman, Nicolás
AU - Lobos, Maite
AU - Arias, Tatiana
AU - Kong, Christina S.
AU - Busaidy, Naifa
AU - Grubbs, Elizabeth G.
AU - Graham, Paul
AU - Stewart, John
AU - Tang, Alice
AU - Wang, Jiang
AU - Orloff, Lisa
AU - Henríquez, Marcela
AU - Lagos, Marcela
AU - Osorio, Miren
AU - Schachter, Dina
AU - Franco, Carmen
AU - Medina, Francisco
AU - Wohllk, Nelson
AU - Diaz, René E.
AU - Veliz, Jesús
AU - Horvath, Eleonora
AU - Tala, Hernán
AU - Pineda, Pedro
AU - Arroyo, Patricia
AU - Vasquez, Félix
AU - Traipe, Eufrosina
AU - Marín, Luis
AU - Miranda, Giovanna
AU - Bruce, Elsa
AU - Bracamonte, Milagros
AU - Mena, Natalia
AU - González, Hernán E.
N1 - Publisher Copyright:
© Mark Zafereo et al. 2020; Published by Mary Ann Liebert, Inc. 2020.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and-2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and-2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and-2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% [95% confidence interval; CI 77-97] and 91% [95% CI 79-98] for TGCT-1 and-2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% [95% CI 82-94] and 87% [95% CI 77-94], respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%. Conclusions: Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.
AB - Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and-2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and-2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and-2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% [95% confidence interval; CI 77-97] and 91% [95% CI 79-98] for TGCT-1 and-2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% [95% CI 82-94] and 87% [95% CI 77-94], respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%. Conclusions: Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.
KW - clinical validation
KW - gene classifier
KW - indeterminate thyroid cytology
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U2 - 10.1089/thy.2019.0490
DO - 10.1089/thy.2019.0490
M3 - Article
C2 - 31910118
AN - SCOPUS:85084694430
SN - 1050-7256
VL - 30
SP - 704
EP - 712
JO - Thyroid
JF - Thyroid
IS - 5
ER -