TY - JOUR
T1 - BRAF V600E confers male sex disease-specific mortality risk in patients with papillary thyroid cancer
AU - Wang, Fei
AU - Zhao, Shihua
AU - Shen, Xiaopei
AU - Zhu, Guangwu
AU - Liu, Rengyun
AU - Viola, David
AU - Elisei, Rossella
AU - Puxeddu, Efisio
AU - Fugazzola, Laura
AU - Colombo, Carla
AU - Jarzab, Barbara
AU - Czarniecka, Agnieszka
AU - Lam, Alfred K.
AU - Mian, Caterina
AU - Vianello, Federica
AU - Yip, Linwah
AU - Riesco-Eizaguirre, Garcilaso
AU - Santisteban, Pilar
AU - O’Neill, Christine J.
AU - Sywak, Mark S.
AU - Clifton-Bligh, Roderick
AU - Bendlova, Bela
AU - Sýkorová, Vlasta
AU - Wang, Yangang
AU - Xing, Mingzhao
N1 - Funding Information:
Supported by US National Institutes of Health (NIH) Grants No. R01CA215142 and R01CA189224 (M.X.) and by the following additional funding at the individual participating centers: Polish National Center of Research and Development MILESTONE (Molecular Diagnostics and Imaging in Individualized Therapy for Breast, Thyroid and Prostate Cancer) Project Grant No. STRATEGMED2/267398/4/NCBR/2015 (A.C., B.J.); grants from the Menzies Health Institute, Griffith University, Queensland Cancer Council, and Queensland Smart State Fellowship in Australia (A.K.L.); Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) Grant No. SAF2016-75531-R, Instituto de Salud Carlos III Grant No. PI14/01980, Asociación Española Contra el Cáncer Foundation Grant No. GCB14142311CRES, and TIRONET2-CM Grant No. B2017/BMD-3724 TIRONET2-CM in Spain (P.S., G.R.-E.); Institute of Endocrinology Grants No. AZV 16-32665A and MH CZ-DRO in the Czech Republic (B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (R.C.-B.) in Australia; National Institute on Aging, NIH, Grant No. 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute in Italy (D.V., R.E.); and Grant No. 13-1-3-58-nsh from the Qingdao Science and Technology Project for People’s Livelihood (F.W., S.Z.), Shandong Outstanding Young Scientist Award Grant No. BS2009YY030 (F.W.), Grant No. 2013 WS0266 from the Health Department of Shandong Province (S.Z., F.W.), and Grant No. 12-1-2-15-jch from the Innovative Platform Project of Qingdao (S.Z., Y.W.) in the People’s Republic of China.
Publisher Copyright:
© 2018 by American Society of Clinical Oncology.
PY - 2018/9/20
Y1 - 2018/9/20
N2 - Purpose To test whether the prognostic risk of male sex in papillary thyroid cancer (PTC) is determined by BRAF V600E and can thus be stratified by BRAF status. Patients and Methods We retrospectively investigated the relationship between male sex and clinicopathologic outcomes in PTC, particularly mortality, with respect to BRAF status in 2,638 patients (male, n = 623; female, n = 2,015) from 11 centers in six countries, with median age of 46 years (interquartile range, 35-58 years) at diagnosis and median follow-up time of 58 months (interquartile range, 26-107 months). Results Distant metastasis rates in men and women were not different in wild-type BRAF PTC but were different in BRAF V600E PTC: 8.9% (24 of 270) and 3.7% (30 of 817; P = .001), respectively. In wild-type BRAF PTC, mortality rates were 1.4% (five of 349) versus 0.9% (11 of 1175) in men versus women (P = .384), with a hazard ratio (HR) of 1.59 (95% CI, 0.55 to 4.57), which remained insignificant at 0.70 (95% CI, 0.23 to 2.09) after clinicopathologic multivariable adjustment. In BRAF V600E PTC, mortality rates were 6.6% (18 of 272) versus 2.9% (24 of 822) in men versus women (P = .006), with an HR of 2.43 (95% CI, 1.30 to 4.53), which remained significant at 2.74 (95% CI, 1.38 to 5.43) after multivariable adjustment. In conventional-variant PTC, male sex similarly had no effect in wild-type BRAF patients; mortality rates in BRAF V600E patients were 7.2% (16 of 221) versus 2.9% (19 of 662) in men versus women (P = .004), with an HR of 2.86 (95% CI, 1.45 to 5.67), which remained significant at 3.51 (95% CI, 1.62 to 7.63) after multivariable adjustment. Conclusion Male sex is a robust independent risk factor for PTC-specific mortality in BRAF V600E patients but not in wild-type BRAF patients. The prognostic risk of male sex in PTC can thus be stratified by BRAF status in clinical application.
AB - Purpose To test whether the prognostic risk of male sex in papillary thyroid cancer (PTC) is determined by BRAF V600E and can thus be stratified by BRAF status. Patients and Methods We retrospectively investigated the relationship between male sex and clinicopathologic outcomes in PTC, particularly mortality, with respect to BRAF status in 2,638 patients (male, n = 623; female, n = 2,015) from 11 centers in six countries, with median age of 46 years (interquartile range, 35-58 years) at diagnosis and median follow-up time of 58 months (interquartile range, 26-107 months). Results Distant metastasis rates in men and women were not different in wild-type BRAF PTC but were different in BRAF V600E PTC: 8.9% (24 of 270) and 3.7% (30 of 817; P = .001), respectively. In wild-type BRAF PTC, mortality rates were 1.4% (five of 349) versus 0.9% (11 of 1175) in men versus women (P = .384), with a hazard ratio (HR) of 1.59 (95% CI, 0.55 to 4.57), which remained insignificant at 0.70 (95% CI, 0.23 to 2.09) after clinicopathologic multivariable adjustment. In BRAF V600E PTC, mortality rates were 6.6% (18 of 272) versus 2.9% (24 of 822) in men versus women (P = .006), with an HR of 2.43 (95% CI, 1.30 to 4.53), which remained significant at 2.74 (95% CI, 1.38 to 5.43) after multivariable adjustment. In conventional-variant PTC, male sex similarly had no effect in wild-type BRAF patients; mortality rates in BRAF V600E patients were 7.2% (16 of 221) versus 2.9% (19 of 662) in men versus women (P = .004), with an HR of 2.86 (95% CI, 1.45 to 5.67), which remained significant at 3.51 (95% CI, 1.62 to 7.63) after multivariable adjustment. Conclusion Male sex is a robust independent risk factor for PTC-specific mortality in BRAF V600E patients but not in wild-type BRAF patients. The prognostic risk of male sex in PTC can thus be stratified by BRAF status in clinical application.
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U2 - 10.1200/JCO.2018.78.5097
DO - 10.1200/JCO.2018.78.5097
M3 - Article
C2 - 30070937
AN - SCOPUS:85053699353
SN - 0732-183X
VL - 36
SP - 2787
EP - 2795
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 27
ER -