Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic bi...Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma （PTMC） is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC （TCVPTMC）, multifocality, extrathyroidal extension （ETE） and lymph node metastasis （LNM）. A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were in- cluded in the meta-analysis, and 1143 （50.7%） of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size （OR： 1.64; 95% CI： 1.16-2.32）, multifocality （OR： 1.58; 95% CI： 1.25-2.00）, ETE （OR： 2.59; 95% CI： 2.03-3.29）, LNM （OR： 1.73; 95% CI： 1.14-2.62）, advanced stage （OR： 2.03; 95% CI： 1.14-3.64） and TCVPTMC （OR： 5.07; 95% CI： 1.49-17.27; P=0.009）. Additionally, the BRAF mutation was found to be not associated with age, gender, con- comitant hashimoto thyroiditis or nodular goiter （P〉0.05 for all）. This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, ad- vanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.展开更多
Despite the promising initial anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs),most advanced non-small-cell lung cancers(NSCLCs)progress eventually due to therapeutic resis...Despite the promising initial anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs),most advanced non-small-cell lung cancers(NSCLCs)progress eventually due to therapeutic resistance.V-Raf murine sarcoma viral oncogene homolog B1(BRAF)^(V600E) mutation has been considered as an uncommon mutation that contributes to acquired resistance for EGFR-TKIs.In the presented case,BRAF^(V600E) mutation was detected as an acquired resistance-mediated mutation in a patient treated with osimertinib(a third-generation EGFR-TKI).The presented patient achieved partial regression and ongoing PFS of four months after the co-inhibition of osimertinib plus dabrafenib(BRAF inhibitor)and trametinib(MEK inhibitor).Our case further enriches the clinical evidence of the efficacy of EGFR/BRAF/MEK co-inhibition in patients with an acquired BRAF^(V600E) mutation,consistent with the review of the literature(eight cases).Additionally,our case highlights the important role of sample type,method,and platform of gene detection in patient management,life quality,and prognosis,as well as the understanding of acquired resistance mechanism.展开更多
文摘Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma （PTMC） is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC （TCVPTMC）, multifocality, extrathyroidal extension （ETE） and lymph node metastasis （LNM）. A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were in- cluded in the meta-analysis, and 1143 （50.7%） of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size （OR： 1.64; 95% CI： 1.16-2.32）, multifocality （OR： 1.58; 95% CI： 1.25-2.00）, ETE （OR： 2.59; 95% CI： 2.03-3.29）, LNM （OR： 1.73; 95% CI： 1.14-2.62）, advanced stage （OR： 2.03; 95% CI： 1.14-3.64） and TCVPTMC （OR： 5.07; 95% CI： 1.49-17.27; P=0.009）. Additionally, the BRAF mutation was found to be not associated with age, gender, con- comitant hashimoto thyroiditis or nodular goiter （P〉0.05 for all）. This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, ad- vanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.
基金This work was supported by the Shanghai Municipal Key Clinical Specialty(shslczdzk02202)the National Natural Science Foundation of China(81672271).
文摘Despite the promising initial anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs),most advanced non-small-cell lung cancers(NSCLCs)progress eventually due to therapeutic resistance.V-Raf murine sarcoma viral oncogene homolog B1(BRAF)^(V600E) mutation has been considered as an uncommon mutation that contributes to acquired resistance for EGFR-TKIs.In the presented case,BRAF^(V600E) mutation was detected as an acquired resistance-mediated mutation in a patient treated with osimertinib(a third-generation EGFR-TKI).The presented patient achieved partial regression and ongoing PFS of four months after the co-inhibition of osimertinib plus dabrafenib(BRAF inhibitor)and trametinib(MEK inhibitor).Our case further enriches the clinical evidence of the efficacy of EGFR/BRAF/MEK co-inhibition in patients with an acquired BRAF^(V600E) mutation,consistent with the review of the literature(eight cases).Additionally,our case highlights the important role of sample type,method,and platform of gene detection in patient management,life quality,and prognosis,as well as the understanding of acquired resistance mechanism.
