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.

BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer / Y. Tao, F. Wang, X. Shen, G. Zhu, R. Liu, D. Viola, R. Elisei, E. Puxeddu, L. Fugazzola, C. Colombo, B. Jarzab, A. Czarniecka, A.K. Lam, C. Mian, F. Vianello, L. Yip, G. Riesco-Eizaguirre, P. Santisteban, C.J. O'Neill, M.S. Sywak, R. Clifton-Bligh, B. Bendlova, V. Sýkorová, S. Zhao, Y. Wang, M. Xing. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. - ISSN 1945-7197. - 106:11(2021), pp. 3228-3238. [10.1210/clinem/dgab286]

BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer

L. Fugazzola;C. Colombo
Membro del Collaboration Group
;
F. Vianello;
2021

Abstract

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.
BRAF mutation; lymph node metastasis; mortality; prognostic molecular marker; risk stratification; thyroid cancer
Settore MED/13 - Endocrinologia
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/968157
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