Yubing Tao1, Fei Wang1,2, Xiaopei Shen2, Guangwu Zhu2, Rengyun Liu2, David Viola3, Rossella Elisei3, Efisio Puxeddu4, Laura Fugazzola5, Carla Colombo5, Barbara Jarzab6, Agnieszka Czarniecka6, Alfred K Lam7, Caterina Mian8, Federica Vianello9, Linwah Yip10, Garcilaso Riesco-Eizaguirre11,12,13, Pilar Santisteban12,13, Christine J O'Neill14, Mark S Sywak14, Roderick Clifton-Bligh14, Bela Bendlova15, Vlasta Sýkorová15, Shihua Zhao1, Yangang Wang1, Mingzhao Xing2. 1. Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, China. 2. Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 4. Department of Medicine, University of Perugia, Perugia, Italy. 5. Division of Endocrinology and Metabolism, IRCCS Istituto Auxologico Italiano, Milan and Department of Pathophysiology and Transplantation, University of Milan, Italy. 6. Maria Sklodowska-Curie National Institute of Oncology, Gliwice Branch, Gliwice,Poland. 7. Cancer Molecular Pathology of School of Medicine, Griffith University-Gold Coast, Australia. 8. Department of Medicine, Endocrinology Unit, University of Padua, Padua, Italy. 9. Veneto Institute of Oncology, IRCCS, Padua, Italy. 10. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 11. Department of Endocrinology and Nutrition Hospital Universitario La Paz and Hospital Universitario de Móstoles, Madrid, Spain. 12. Biomedical Research Institute "Alberto Sols," Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain. 13. Ciberonc, Health Institute Carlos III, Madrid, Spain. 14. Endocrine Surgical Unit, University of Sydney, Sydney, Australia. 15. Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
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.
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.
Authors: Daniel Mankarios; Peter Baade; Pip Youl; Robin H Mortimer; Adedayo A Onitilo; Anthony Russell; Suhail A R Doi Journal: Endocrine Date: 2013-10-31 Impact factor: 3.633
Authors: Julio Ricarte-Filho; Ian Ganly; Michael Rivera; Nora Katabi; Weimin Fu; Ashok Shaha; R Michael Tuttle; James A Fagin; Ronald Ghossein Journal: Thyroid Date: 2012-04-03 Impact factor: 6.568
Authors: Mingzhao Xing; Ali S Alzahrani; Kathryn A Carson; David Viola; Rossella Elisei; Bela Bendlova; Linwah Yip; Caterina Mian; Federica Vianello; R Michael Tuttle; Eyal Robenshtok; James A Fagin; Efisio Puxeddu; Laura Fugazzola; Agnieszka Czarniecka; Barbara Jarzab; Christine J O'Neill; Mark S Sywak; Alfred K Lam; Garcilaso Riesco-Eizaguirre; Pilar Santisteban; Hirotaka Nakayama; Ralph P Tufano; Sara I Pai; Martha A Zeiger; William H Westra; Douglas P Clark; Roderick Clifton-Bligh; David Sidransky; Paul W Ladenson; Vlasta Sykorova Journal: JAMA Date: 2013-04-10 Impact factor: 56.272