Patient age-associated mortality risk is differentiated by BRAF V600E status in papillary thyroid cancer

Xiaopei Shen, Guangwu Zhu, Rengyun Liu, 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. ONeill, Mark S. Sywak, Roderick Clifton-Bligh, Bela Bendlova & 2 others Vlasta Sykorova, Michael Mingzhao Xing

Research output: Contribution to journalArticle

Abstract

Purpose For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor. Patients and Methods We conducted a comparative study of the relationship between patient age at diagnosis and PTCspecific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study. Results There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed. Conclusion The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number5
DOIs
StatePublished - Feb 10 2018

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Mortality
Papillary Thyroid cancer
Mutation
Risk Management
Kaplan-Meier Estimate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Patient age-associated mortality risk is differentiated by BRAF V600E status in papillary thyroid cancer. / Shen, Xiaopei; Zhu, Guangwu; Liu, Rengyun; 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; ONeill, Christine J.; Sywak, Mark S.; Clifton-Bligh, Roderick; Bendlova, Bela; Sykorova, Vlasta; Xing, Michael Mingzhao.

In: Journal of Clinical Oncology, Vol. 36, No. 5, 10.02.2018, p. 438-445.

Research output: Contribution to journalArticle

Shen, X, Zhu, G, Liu, R, 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, ONeill, CJ, Sywak, MS, Clifton-Bligh, R, Bendlova, B, Sykorova, V & Xing, MM 2018, 'Patient age-associated mortality risk is differentiated by BRAF V600E status in papillary thyroid cancer', Journal of Clinical Oncology, vol. 36, no. 5, pp. 438-445. https://doi.org/10.1200/JCO.2017.74.5497
Shen, Xiaopei ; Zhu, Guangwu ; Liu, Rengyun ; 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 ; ONeill, Christine J. ; Sywak, Mark S. ; Clifton-Bligh, Roderick ; Bendlova, Bela ; Sykorova, Vlasta ; Xing, Michael Mingzhao. / Patient age-associated mortality risk is differentiated by BRAF V600E status in papillary thyroid cancer. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 5. pp. 438-445.
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abstract = "Purpose For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor. Patients and Methods We conducted a comparative study of the relationship between patient age at diagnosis and PTCspecific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study. Results There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed. Conclusion The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC.",
author = "Xiaopei Shen and Guangwu Zhu and Rengyun Liu 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 ONeill, {Christine J.} and Sywak, {Mark S.} and Roderick Clifton-Bligh and Bela Bendlova and Vlasta Sykorova and Xing, {Michael Mingzhao}",
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TY - JOUR

T1 - Patient age-associated mortality risk is differentiated by BRAF V600E status in papillary thyroid cancer

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 - ONeill, Christine J.

AU - Sywak, Mark S.

AU - Clifton-Bligh, Roderick

AU - Bendlova, Bela

AU - Sykorova, Vlasta

AU - Xing, Michael Mingzhao

PY - 2018/2/10

Y1 - 2018/2/10

N2 - Purpose For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor. Patients and Methods We conducted a comparative study of the relationship between patient age at diagnosis and PTCspecific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study. Results There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed. Conclusion The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC.

AB - Purpose For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor. Patients and Methods We conducted a comparative study of the relationship between patient age at diagnosis and PTCspecific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study. Results There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed. Conclusion The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC.

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