TY - JOUR
T1 - BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer
AU - Tao, Yubing
AU - Wang, Fei
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 - Zhao, Shihua
AU - Wang, Yangang
AU - Xing, Mingzhao
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Context: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. Objective: To study whether BRAF V600E affected LNM-associated mortality in PTC. Design, Setting, and Participants: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. Results: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. Conclusions: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.
AB - Context: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. Objective: To study whether BRAF V600E affected LNM-associated mortality in PTC. Design, Setting, and Participants: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. Results: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. Conclusions: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.
KW - BRAF mutation
KW - lymph node metastasis
KW - mortality
KW - prognostic molecular marker
KW - risk stratification
KW - thyroid cancer
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U2 - 10.1210/clinem/dgab286
DO - 10.1210/clinem/dgab286
M3 - Article
C2 - 34273152
AN - SCOPUS:85119470923
SN - 0021-972X
VL - 106
SP - 3228
EP - 3238
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -