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  • BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment

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    Accepted Manuscript (AM)
    Author(s)
    Huang, Yueye
    Qu, Shen
    Zhu, Guangwu
    Wang, Fei
    Liu, Rengyun
    Shen, Xiaopei
    Viola, David
    Elisei, Rossella
    Puxeddu, Efisio
    Fugazzola, Laura
    Colombo, Carla
    Jarzab, Barbara
    Czarniecka, Agnieszka
    Lam, Alfred K
    Mian, Caterina
    Vianello, Federica
    Yip, Linwah
    Riesco-Eizaguirre, Garcilaso
    Santisteban, Pilar
    O'Neill, Christine J
    Xing, Mingzhao
    Griffith University Author(s)
    Lam, Alfred K.
    Year published
    2018
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    Abstract
    Background: Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined. Methods: A genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow–up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher’s exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect ...
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    Background: Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined. Methods: A genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow–up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher’s exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect of BRAF mutation on the recurrence was analyzed by Cox regression and Cox proportional hazard analyses. All statistical tests were two-sided. Results: Recurrence of SI-PTC larger than 1.0 cm and 4.0 cm or less was 9.5% (21/221) vs 3.4% (11/319) in BRAF mutation vs wild-type BRAF patients, with a hazard ratio (HR) of 3.03 (95% confidence interval [CI] = 1.46 to 6.30) and a patient age- and sex-adjusted hazard ratio of 3.10 (95% CI = 1.49 to 6.45, P = .002). Recurrence rates of SI-PTC larger than 2.0 cm and 4.0 cm or less were 16.5% (13/79) vs 3.6% (5/139) in mutation vs wild-type patients (HR = 5.44, 95% CI = 1.93 to 15.34; and adjusted HR = 5.58, 95% CI = 1.96 to 15.85, P = .001). Recurrence rates of SI-PTC larger than 3.0 cm and 4 cm or less were 30.0% (6/20) vs 1.9% (1/54) in mutation vs wild-type patients (HR = 18.40, 95% CI = 2.21 to 152.98; and adjusted HR = 14.73, 95% CI = 1.74 to 124.80, P = .01). Recurrences of mutation-positive SI-PTC were comparable with those of counterpart invasive solitary PTC, around 20% to 30%, in tumors larger than 2.0 cm to 3.0 cm. BRAF mutation was associated with a statistically significant decrease in recurrence-free patient survival on KM analysis, particularly in SI-PTC larger than 2.0 cm and 4.0 cm or less. Similar results were obtained in conventional SI-PTC. The negative predictive values of BRAF mutation for recurrence were 97.8% (95% CI = 96.3% to 98.8%) for general SI-PTC and 98.2% (95% CI = 96.3% to 99.3%) for conventional SI-PTC. Conclusions: BRAF V600E identifies a subgroup of SI-PTC larger than 1.0 cm and 4.0 cm or less, particularly tumors larger than 2.0 cm and 4.0 cm or less, that has high risk for recurrence comparable with that of invasive solitary PTC, making more aggressive treatment reasonable.
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    Journal Title
    JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
    Volume
    110
    Issue
    4
    DOI
    https://doi.org/10.1093/jnci/djx227
    Copyright Statement
    © 2018 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of the National Cancer Institute (JNCI) following peer review. The definitive publisher-authenticated version BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment, Journal of the National Cancer Institute (JNCI), Volume 110, Issue 4, April 2018, Pages 362–370, is available online at: https://doi.org/10.1093/jnci/djx227
    Subject
    Oncology and carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/383342
    Collection
    • Journal articles

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