Mingzhao Xing1, Ali S Alzahrani2, Kathryn A Carson2, Young Kee Shong2, Tae Yong Kim2, David Viola2, Rossella Elisei2, Bela Bendlová2, Linwah Yip2, Caterina Mian2, Federica Vianello2, R Michael Tuttle2, Eyal Robenshtok2, James A Fagin2, Efisio Puxeddu2, Laura Fugazzola2, Agnieszka Czarniecka2, Barbara Jarzab2, Christine J O'Neill2, Mark S Sywak2, Alfred K Lam2, Garcilaso Riesco-Eizaguirre2, Pilar Santisteban2, Hirotaka Nakayama2, Roderick Clifton-Bligh2, Giovanni Tallini2, Elizabeth H Holt2, Vlasta Sýkorová2. 1. Mingzhao Xing and Ali S. Alzahrani, Johns Hopkins University School of Medicine; Kathryn A. Carson, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; Young Kee Shong and Tae Yong Kim, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; David Viola and Rossella Elisei, WHO Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders, University of Pisa, Pisa; Caterina Mian, University of Padua; Federica Vianello, Veneto Institute of Oncology, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua; Efisio Puxeddu, University of Perugia, Perugia; Laura Fugazzola, University of Milan and Fondazione IRCCS CàGranda, Milan; Giovanni Tallini, University of Bologna School of Medicine, Bellaria Hospital, Bologna, Italy; Bela Bendlová and Vlasta Sýkorová, Institute of Endocrinology, Prague, Czech Republic; Linwah Yip, University of Pittsburgh School of Medicine, Pittsburgh, PA; R. Michael Tuttle, Eyal Robenshtok, and James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Agnieszka Czarniecka and Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Christine J. O'Neill, Mark S. Sywak, and Roderick Clifton-Bligh, University of Sydney, Sydney, New South Wales; Alfred K. Lam, Griffith University School of Medicine, Gold Coast, Queensland, Australia; Garcilaso Riesco-Eizaguirre, Hospital La Paz, Health Research Institute, and Hospital Universitario de Móstoles; Garcilaso Riesco-Eizaguirre and Pilar Santisteban, Biomedical Research Institute Alberto Sols, Spanish Council of Research, and Autonomous University of Madrid, Madrid, Spain; Hirotaka Nakayama, Kanagawa Cancer Center, Yokohama, Japan; and Elizabeth H. Holt, Yale University School of Medicine, New Haven, CT. mxing1@jhmi.edu. 2. Mingzhao Xing and Ali S. Alzahrani, Johns Hopkins University School of Medicine; Kathryn A. Carson, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; Young Kee Shong and Tae Yong Kim, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; David Viola and Rossella Elisei, WHO Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders, University of Pisa, Pisa; Caterina Mian, University of Padua; Federica Vianello, Veneto Institute of Oncology, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua; Efisio Puxeddu, University of Perugia, Perugia; Laura Fugazzola, University of Milan and Fondazione IRCCS CàGranda, Milan; Giovanni Tallini, University of Bologna School of Medicine, Bellaria Hospital, Bologna, Italy; Bela Bendlová and Vlasta Sýkorová, Institute of Endocrinology, Prague, Czech Republic; Linwah Yip, University of Pittsburgh School of Medicine, Pittsburgh, PA; R. Michael Tuttle, Eyal Robenshtok, and James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Agnieszka Czarniecka and Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Christine J. O'Neill, Mark S. Sywak, and Roderick Clifton-Bligh, University of Sydney, Sydney, New South Wales; Alfred K. Lam, Griffith University School of Medicine, Gold Coast, Queensland, Australia; Garcilaso Riesco-Eizaguirre, Hospital La Paz, Health Research Institute, and Hospital Universitario de Móstoles; Garcilaso Riesco-Eizaguirre and Pilar Santisteban, Biomedical Research Institute Alberto Sols, Spanish Council of Research, and Autonomous University of Madrid, Madrid, Spain; Hirotaka Nakayama, Kanagawa Cancer Center, Yokohama, Japan; and Elizabeth H. Holt, Yale University School of Medicine, New Haven, CT.
Abstract
PURPOSE: To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). PATIENTS AND METHODS: This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). RESULTS: The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation-positive and 11.6% (125 of 1,082) of BRAF V600E mutation-negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation-positive versus -negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation-positive versus -negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. CONCLUSION: This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories.
PURPOSE: To investigate the prognostic value of BRAFV600E mutation for the recurrence of papillary thyroid cancer (PTC). PATIENTS AND METHODS: This was a retrospective multicenter study of the relationship between BRAFV600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). RESULTS: The overall BRAFV600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAFV600E mutation-positive and 11.6% (125 of 1,082) of BRAFV600E mutation-negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation-positive versus -negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation-positive versus -negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. CONCLUSION: This large multicenter study demonstrates an independent prognostic value of BRAFV600E mutation for PTC recurrence in various clinicopathologic categories.
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