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dc.contributor.authorHuang, Yueye
dc.contributor.authorQu, Shen
dc.contributor.authorZhu, Guangwu
dc.contributor.authorWang, Fei
dc.contributor.authorLiu, Rengyun
dc.contributor.authorShen, Xiaopei
dc.contributor.authorViola, David
dc.contributor.authorElisei, Rossella
dc.contributor.authorPuxeddu, Efisio
dc.contributor.authorFugazzola, Laura
dc.contributor.authorColombo, Carla
dc.contributor.authorJarzab, Barbara
dc.contributor.authorCzarniecka, Agnieszka
dc.contributor.authorLam, Alfred K
dc.contributor.authorMian, Caterina
dc.contributor.authorVianello, Federica
dc.contributor.authorYip, Linwah
dc.contributor.authorRiesco-Eizaguirre, Garcilaso
dc.contributor.authorSantisteban, Pilar
dc.contributor.authorO'Neill, Christine J
dc.contributor.authorXing, Mingzhao
dc.date.accessioned2019-07-05T12:31:30Z
dc.date.available2019-07-05T12:31:30Z
dc.date.issued2018
dc.identifier.issn0027-8874
dc.identifier.doi10.1093/jnci/djx227
dc.identifier.urihttp://hdl.handle.net/10072/383342
dc.description.abstractBackground: 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherOXFORD UNIV PRESS INC
dc.relation.ispartofpagefrom362
dc.relation.ispartofpageto370
dc.relation.ispartofissue4
dc.relation.ispartofjournalJNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
dc.relation.ispartofvolume110
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode1112
dc.titleBRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionPost-print
gro.rights.copyright© 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
gro.hasfulltextFull Text
gro.griffith.authorLam, Alfred K.


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