| PURPOSE To investigate whether lymph node metastasis(LNM)is truly a general mortality risk in papillary thyroid cancer(PTC),particularly conventional PTC(CPTC).To investigate how the BRAF V600 E status may affect lymph node metastasis(LNM)-related mortality risk in papillary thyroid cancer(PTC).To further clarify the risk stratification of disease prognosis,so as to provide patients appropriate treatment methods.PATIENTS AND METHODS(1)The study retrospectively investigated the relationship between LNM and mortality in PTC,especially mortality,with respect to BRAF status in 2638 patients(2015 females and 623 males)from 11 centers in 6countries,with median age of 46(interquartile range,35–58)years at diagnosis and median follow-up time of 58(IQR 26–107)months.These patients were all treated with total or near-total thyroidectomy and pathologically diagnosed of PTC.(2)The study included current known risk factors and outcome factors of PTC,such as age(especially advanced patient age),gender,tumor size,tumor stage,extra thyroid extension,lymph node metastasis,distant metastasis,multifocality,recurrence,mortality.(3)Using SPSS 22.0 software for statistical analysis.Categorical variables were compared using the Pearson chi-square test and the Fisher's exact test was used for case number?5.Comparison of median and interquartile range(IQR)of continuous variables in nonparametric independent samples was performed using Wilcoxon-Mann-Whitney test.Survival probability was calculated by Kaplan-Meier analysis and log-rank test was usd to compare the differences.Effects of univariate and multivariate factors on disease recurrence and patient mortality were compared using Cox regression and Cox proportional hazards analyses,with calculation of hazard ratios(HR)and 95% confidence interval(CI).P < 0.05 was considered significant.RESULTS On the analysis of the entire cohort,In wild-type BRAF patients,mortality rates were 3/1056(0.3%)in non-LNM versus 13/449(2.9%)in LNM patients,corresponding to HR remained significant after multivariate adjustment.In BRAF-mutant patients,it showd the same result.LNM showd mortality risk in both wild-type BRAF patients and BRAF-mutant patients.On the analysis of conventional PTC(CPTC),which accounts for the vast majority of PTCs,LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF-mutant patients;mortality rates were 2/659(0.3%)versus4/321(1.2%)in non-LNM versus LNM patients(P=0.094),respectively,in wild-type BRAF patients,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-mutant CPTC,morality rates were 7/515(1.4%)versus 28/363(7.7%)in non-LNM versus LNM patients(P<0.001),respectively,corresponding to 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 mutation versus absence of both was 27.39(5.15-145.80),with Kaplan-Meier analyses showing a similar synergism.CONCLUSION Lymph node metastasis and BRAF V600 E mutation are risk factors of PTC.LNM-related mortality risk is sharply differentiated by the BRAF status in PTC,particularly CPTC,showing no increased mortality risk in wild-type BRAF patients but a robust one in BRAF-mutant patients.If there is no BRAF V600 E mutation,the prognosis of patients which have LNM are still good.If someone is dignosed have BRAF V600 E mutation and also combine with lymph node metastasis,the mortality is significantly higher than patients without LNM.Management of LNM in PTC may thus be guided by the BRAF mutation status. |
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