{"doi":"10.1210/clinem/dgab286","title":"<i>BRAF</i> V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer","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.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":153580,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8973,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":651373,"name":"Fei Wang","orcid":"0000-0001-8308-0269","position":1,"is_corresponding":false},{"id":651374,"name":"Xiaopei Shen","orcid":"0000-0002-0004-4228","position":2,"is_corresponding":false},{"id":457706,"name":"Guangwu Zhu","orcid":"0000-0003-2533-7171","position":3,"is_corresponding":false},{"id":457705,"name":"Rengyun Liu","orcid":"0000-0002-1408-2372","position":4,"is_corresponding":false},{"id":651375,"name":"David Viola","orcid":"0000-0001-7683-152X","position":5,"is_corresponding":false},{"id":651376,"name":"Rossella Elisei","orcid":"0000-0002-5333-9257","position":6,"is_corresponding":false},{"id":651377,"name":"Efisio Puxeddu","orcid":"0000-0001-9611-6216","position":7,"is_corresponding":false},{"id":651378,"name":"Laura Fugazzola","orcid":"0000-0001-5372-0982","position":8,"is_corresponding":false},{"id":620301,"name":"Carla Colombo","orcid":"0000-0002-8975-695X","position":9,"is_corresponding":false},{"id":651379,"name":"Barbara Jarząb","orcid":"0000-0001-9811-9584","position":10,"is_corresponding":false},{"id":651380,"name":"Agnieszka Czarniecka","orcid":"0000-0003-1249-7205","position":11,"is_corresponding":false},{"id":91076,"name":"Alfred King-Yin Lam","orcid":"0000-0003-2771-564X","position":12,"is_corresponding":false},{"id":651381,"name":"Caterina Mian","orcid":"0000-0003-2615-8001","position":13,"is_corresponding":false},{"id":651382,"name":"Federica Vianello","orcid":"0000-0001-7801-5825","position":14,"is_corresponding":false},{"id":398050,"name":"Linwah Yip","orcid":"0000-0002-2449-3685","position":15,"is_corresponding":false},{"id":651383,"name":"Garcilaso Riesco‐Eizaguirre","orcid":"0000-0002-2608-6397","position":16,"is_corresponding":false},{"id":289725,"name":"Pilar Santisteban","orcid":"0000-0002-2758-796X","position":17,"is_corresponding":false},{"id":651384,"name":"Christine J. 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