BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma

Kyeong J. Kim, Sin G. Kim, Jie Tan, Xiaopei Shen, David Viola, Rossella Elisei, Efisio Puxeddu, Laura Fugazzola, Carla Colombo, Barbara Jarzab, Agnieszka Czarniecka, Alfred K. Lam, Caterina Mian, Federica Vianello, Linwah Yip, Garcilaso Riesco-Eizaguirre, Pilar Santisteban, Christine J. O'Neill, Mark S. Sywak, Roderick Clifton-BlighBela Bendlova, Vlasta Sýkorová, Mingzhao Xing

Research output: Contribution to journalArticle

Abstract

Introduction: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management. Methods: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months). Results: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC. Conclusions: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalEuropean Journal of Cancer
Volume124
DOIs
StatePublished - Jan 2020

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Decision Making
Mutation
Recurrence
Papillary Thyroid Microcarcinoma
Confidence Intervals
Thyroidectomy
Multicenter Studies
Survival
Neoplasms

Keywords

  • Active surveillance
  • BRAF V600E mutation
  • Papillary thyroid microcarcinoma
  • Prognosis
  • Risk stratification

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma. / Kim, Kyeong J.; Kim, Sin G.; Tan, Jie; 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.; Sywak, Mark S.; Clifton-Bligh, Roderick; Bendlova, Bela; Sýkorová, Vlasta; Xing, Mingzhao.

In: European Journal of Cancer, Vol. 124, 01.2020, p. 161-169.

Research output: Contribution to journalArticle

Kim, KJ, Kim, SG, Tan, J, Shen, X, Viola, D, Elisei, R, Puxeddu, E, Fugazzola, L, Colombo, C, Jarzab, B, Czarniecka, A, Lam, AK, Mian, C, Vianello, F, Yip, L, Riesco-Eizaguirre, G, Santisteban, P, O'Neill, CJ, Sywak, MS, Clifton-Bligh, R, Bendlova, B, Sýkorová, V & Xing, M 2020, 'BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma', European Journal of Cancer, vol. 124, pp. 161-169. https://doi.org/10.1016/j.ejca.2019.10.017
Kim, Kyeong J. ; Kim, Sin G. ; Tan, Jie ; 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. ; Sywak, Mark S. ; Clifton-Bligh, Roderick ; Bendlova, Bela ; Sýkorová, Vlasta ; Xing, Mingzhao. / BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma. In: European Journal of Cancer. 2020 ; Vol. 124. pp. 161-169.
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abstract = "Introduction: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management. Methods: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months). Results: On overall analyses of all PTMCs, tumour recurrences were 6.4{\%} (32/502) versus 10.8{\%} (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95{\%} CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3{\%} (5/383) versus 4.3{\%} (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95{\%} CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC. Conclusions: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.",
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author = "Kim, {Kyeong J.} and Kim, {Sin G.} and Jie Tan and Xiaopei Shen and David Viola and Rossella Elisei and Efisio Puxeddu and Laura Fugazzola and Carla Colombo and Barbara Jarzab and Agnieszka Czarniecka and Lam, {Alfred K.} and Caterina Mian and Federica Vianello and Linwah Yip and Garcilaso Riesco-Eizaguirre and Pilar Santisteban and O'Neill, {Christine J.} and Sywak, {Mark S.} and Roderick Clifton-Bligh and Bela Bendlova and Vlasta S{\'y}korov{\'a} and Mingzhao Xing",
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T1 - BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma

AU - Kim, Kyeong J.

AU - Kim, Sin G.

AU - Tan, Jie

AU - Shen, Xiaopei

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 - Xing, Mingzhao

PY - 2020/1

Y1 - 2020/1

N2 - Introduction: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management. Methods: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months). Results: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC. Conclusions: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.

AB - Introduction: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management. Methods: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months). Results: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC. Conclusions: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.

KW - Active surveillance

KW - BRAF V600E mutation

KW - Papillary thyroid microcarcinoma

KW - Prognosis

KW - Risk stratification

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