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.

• Klíčová slova
• BRAF mutation, lymph node metastasis, mortality, prognostic molecular marker, risk stratification, thyroid cancer,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   mortalita   patologie   MeSH
• lymfatické metastázy MeSH
• míra přežití MeSH
• mutace * MeSH
• nádorové biomarkery genetika   MeSH
• nádory štítné žlázy genetika   mortalita   patologie   MeSH
• následné studie MeSH
• papilární karcinom štítné žlázy genetika   mortalita   sekundární   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny B-Raf MeSH

Radioiodine (131 I, RAI) has traditionally been used in thyroid cancer treatment but its benefit should be balanced against possible risks. Among them, salivary gland dysfunction has often been discussed, although the reported data have been inconsistent. The aim of our prospective study was to evaluate salivary gland function in 31 thyroidectomised patients (6 men, 25 women; median age 52 yr) before and 4-6 months after RAI remnant ablation (RRA), using activity of 3.7 GBq 131 I-NaI. Salivary gland uptake and excretion fractions were quantitatively assessed with 99m Tc - pertechnetate salivary gland scintigraphy. Pre- and post-treatment values were compared using Wilcoxon signed rank test. No statistically significant difference in the pre- and post-treatment values was observed in parotid or submandibular glands uptake, or in the parotid or submandibular excretion fractions. The calculated power for minimum relevant difference of 25% with the sample size of 31 ranged between 86% and 96% for the individual variables, making our negative results reasonably reliable. The results suggest that RRA with the most commonly used activity of 3.7 GBq has no important impact on salivary gland function. Therefore, the concerns about putative salivary gland functional deterioration following RRA are probably unjustified.

• Klíčová slova
• 99mTc - pertechnetate, radioiodine remnant ablation, salivary gland dynamic scintigraphy, thyroid cancer, xerostomia,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy * diagnostické zobrazování   radioterapie   MeSH
• podčelistní slinná žláza MeSH
• prospektivní studie MeSH
• radioisotopová scintigrafie MeSH
• radioizotopy jodu MeSH
• slinné žlázy diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• radioizotopy jodu MeSH

BACKGROUND: Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined. METHODS: A genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow-up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher's exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect of BRAF mutation on the recurrence was analyzed by Cox regression and Cox proportional hazard analyses. All statistical tests were two-sided. RESULTS: Recurrence of SI-PTC larger than 1.0 cm and 4.0 cm or less was 9.5% (21/221) vs 3.4% (11/319) in BRAF mutation vs wild-type BRAF patients, with a hazard ratio (HR) of 3.03 (95% confidence interval [CI] = 1.46 to 6.30) and a patient age- and sex-adjusted hazard ratio of 3.10 (95% CI = 1.49 to 6.45, P = .002). Recurrence rates of SI-PTC larger than 2.0 cm and 4.0 cm or less were 16.5% (13/79) vs 3.6% (5/139) in mutation vs wild-type patients (HR = 5.44, 95% CI = 1.93 to 15.34; and adjusted HR = 5.58, 95% CI = 1.96 to 15.85, P = .001). Recurrence rates of SI-PTC larger than 3.0 cm and 4 cm or less were 30.0% (6/20) vs 1.9% (1/54) in mutation vs wild-type patients (HR = 18.40, 95% CI = 2.21 to 152.98; and adjusted HR = 14.73, 95% CI = 1.74 to 124.80, P = .01). Recurrences of mutation-positive SI-PTC were comparable with those of counterpart invasive solitary PTC, around 20% to 30%, in tumors larger than 2.0 cm to 3.0 cm. BRAF mutation was associated with a statistically significant decrease in recurrence-free patient survival on KM analysis, particularly in SI-PTC larger than 2.0 cm and 4.0 cm or less. Similar results were obtained in conventional SI-PTC. The negative predictive values of BRAF mutation for recurrence were 97.8% (95% CI = 96.3% to 98.8%) for general SI-PTC and 98.2% (95% CI = 96.3% to 99.3%) for conventional SI-PTC. CONCLUSIONS: BRAF V600E identifies a subgroup of SI-PTC larger than 1.0 cm and 4.0 cm or less, particularly tumors larger than 2.0 cm and 4.0 cm or less, that has high risk for recurrence comparable with that of invasive solitary PTC, making more aggressive treatment reasonable.

• MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• individualizovaná medicína * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   patologie   MeSH
• míra přežití MeSH
• mutace * MeSH
• nádorové biomarkery genetika   MeSH
• nádory štítné žlázy genetika   patologie   MeSH
• následné studie MeSH
• papilární karcinom genetika   patologie   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny B-Raf MeSH

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.

• MeSH
• dospělí MeSH
• hodnocení rizik metody   statistika a číselné údaje   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• missense mutace * MeSH
• nádory štítné žlázy genetika   patologie   MeSH
• následné studie MeSH
• papilární karcinom genetika   patologie   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf MeSH