The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors.

INTRODUCTION: The risk of over-treatment in low-advanced PTC stages has prompted clinicians to search for new reliable prognostic factors. The presence of BRAF mutation, the most frequent molecular event in PTC, seems to be a good candidate. However, there is still lack of randomised trials and its significance has been proved by retrospective analyses, involving a large group of patients. The question arises whether this factor is useful in smaller populations, characterised for specialised centres. Thus, the aim of the study was to evaluate the use of BRAF mutation as a potential predictive marker in PTC patients. MATERIAL: 233 PTC subjects treated between 2004-2006, were retrospectively analysed. Stage pT1 was diagnosed in 64.8% patients and lymph node metastases in 30.9%. Median follow-up was 7.5 years. BRAFV600E mutation was assessed postoperatively in all cases. RESULTS: BRAF V600E mutation was found in 54.5%. It was more frequent in patients > 45 years (p=0.0001), and associated with larger tumour size (p=0.004). Patients with tumours <= 10 mm were over-represented among BRAF negative population (p=0.03). No association between BRAF mutation and other clinicopathological factors was observed. BRAF status was associated neither with relapse nor with disease-free survival (DFS) (p=0.76). Nodal status, extrathyroidal invasion and tumour size significantly influenced DFS. CONCLUSION: The risk of PTC recurrence is mainly related to the presence of lymph node metastases and extrathyroidal invasion, whereas no impact of BRAF V600E mutation has been demonstrated.

Has differentiated thyroid cancer (DTC) staging changed with in the last ten years in the Silesia region of Poland?

INTRODUCTION: The aim of the study was to compare the advancement of thyroid cancer at diagnosis in Polish patients from the Silesian district in the years 1999 and 2008. MATERIAL AND METHODS: The analyzed group consisted of Silesian district patients with thyroid cancer, who were registered by the Department of Tumour Epidemiology of the Institute of Oncology in Gliwice in the years 1999 and 2008. From a group of 186 patients who entered on record in 1999, 167 were qualified for this analysis. Similarly, from 238 patients registered in 2008, finally 226 were added. We analyzed: sex, age at diagnosis, histotype of thyroid cancer, and DTC staging according to TNM (UICC 2002). In 1999 there were 137 females (82.04 %) and 30 males (17.93%) with thyroid cancer diagnosed at ages 5-81 years. In 2008 there were 183 females (80.97%) and 43 males (19.03%) diagnosed at ages 14-80 years. In both groups, in 1999 and 2008, the median age was the same (51 years). RESULTS: In the year 1999, 119 (71%) and in 2008, 197 (87%) patients were diagnosed with papillary thyroid cancer (p = 0.0003). Relations between age and sex were similar in these years. There was some increase in frequency of patients diagnosed with papillary microcancer (pT1a), which was on the border of statistical significance (p = 0.05). A statistically significant increase of pT1 (p = 0.02) and decrease of pT4 (p = 0.001) and of pTx (p = 0.002) was observed in the year 2008 in the whole cohort of DTC patients. CONCLUSIONS: 1. In 2008 the contribution of papillary histotype to all thyroid cancer patients (87%) was significantly higher than in 1999. 2. The percentage of DTC patients diagnosed with pT1 disease was significantly higher in 2008.

Prognostic value of lymph node metastases of differentiated thyroid cancer (DTC) according to the local advancement and range of surgical excision.

UNLABELLED: : In differentiated thyroid carcinoma (DTC) with primary tumor smaller than 1 cm, the routine central lymph node (LN) dissection is questioned, due to increased risk of post-surgery complications and lack of confirmed benefit. AIM: The analysis of prognostic significance of LN metastases, in DTC patients to verify the potential role of central neck lymphadenectomy on disease staging. MATERIALS AND METHODS: The group of 195 DTC patients, primarily operated between 2004 and 2005, was retrospectively analyzed. 184 patients after radical operation, with no distant metastases diagnosed before surgery, were included into analysis. LN metastases were observed in 55 of cases (28%). In 124 cases only dissection of central LN compartment was performed, in 36 patients also uni- or bilateral modified cervical lymphadectomy was carried out. In 24 patients with tumor limited to the thyroid gland without suspicious lymph nodes, the routine central lymph node dissection was not done. RESULTS: Median follow-up was 4 years. The 5-year overall and disease free survival standardized ratio were 100% and 95% respectively. The risk of LN metastases increased with the more locally advanced cancer. In the group of 124 patients, in whom only central LN dissection was performed, LN metastases were diagnosed in 15 cases (12%). No significant relation between multifocality and frequency of central and/or lateral LN metastases was noticed. Significant correlation between N feature and extrathyroidal invasion was observed (p = 0,0003). The presence of LN metastases was related to worsening of disease free survival from 99 to 90%. During the follow-up recurrence occurred in 6 (3%) cases. In 24 patients in whom only total thyroidectomy was done, no local or distant recurrence was observed. The assessment of early postoperative complications (hypoparathyroidism, paresis of vocal cords) indicated that the frequency of early calcium balance disturbances was significantly lower in patients in whom central LN dissection was not performed (p = 0,04) CONCLUSIONS: Our result indicate that in the early diagnosis of thyroid cancer, the occurrence of LN DTC metastases is rarer and was observed only in 12% of elective dissections of central LN node compartment, if no lateral dissection was indicated due to the lack of clinical suspicion. In DTC patients with tumor diameter <1 cm and no sonographical or inraoperative suspicion on LN involvement, routine central lymphadenectomy may be not obligatory.

[Evaluation of the therapeutic benefits in relation to the extent of surgery in patients with differentiated thyroid carcinoma]. / Ocena korzysci terapeutycznych z zastosowania okreslonego zakresu operacji u chorych na zrósnicowane raki tarczycy.

INTRODUCTION: Evaluation of the therapeutic benefits in relation to the stage of thyroid cancer and to the extent of surgery and the risk of postoperative complications. MATERIAL AND METHODS: Retrospective analysis of differentiated thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of them were treated or diagnosed in Institute of Oncology in Gliwice between 1986-1998. Previously they were operated in various surgical centers all-over Poland. The risk of death, local relapse and postoperative complications were analyzed using the decisiontree model to evaluate the therapeutic benefits. RESULTS: The recurrent laryngeal nerve injury (transient or permanent) was observed in retrospective analysis in 21% of patients, while postoperative hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in patients treated by less than total thyroidectomy). The advantage of radical surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in patients treated by total thyroidectomy and 0.69 in those who received less extensive operation. CONCLUSIONS: The analysis of therapeutic benefits confirmed the limit of 1 cm tumor diameter between less extensive surgery and total thyroidectomy. It showed that total thyroidectomy brings a significant therapeutic benefits in patients in > T1M0 stage. The improvement of overall survival and decrease of local relapse far outweigh the disadvantages related to postoperative complications.

[The impact of the extent and time of operation on the survival in patients with differentiated thyroid carcinoma (DTC)]. / Znaczenie zakresu i czasu leczenia operacyjnego u chorych na zróznicowane raki tarczycy.

INTRODUCTION: To analyze the impact of time and extent of operation on overall and disease-free survival in patients with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS: Retrospective analysis of 1235 DTC patients, a representative probe of patients diagnosed or treated between 1986 to 1998 was performed. 277 patients were staged T1M0 and 958 ones staged > T1M0. 10-year outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard model. RESULTS: The T1M0 patients were characterized by the best overall and disease-free survival independently of the time and the extent of operation (98% and 96% respectively); in > T1M0 group the survival was better in patients who were treated by total thyroidectomy (94% and 68% respectively) than in patients treated by non-total thyroidectomy (78% and 47% respectively). In patients treated by completion of total thyroidectomy delayed more than 1 year post cancer diagnosis the incidence of carcinoma in postoperative pathological material was twice as high in comparison to the group in whom total thyroidectomy was performed within the first year of therapy (p = 0.000). CONCLUSIONS: 1. In differentiated thyroid carcinoma the prognosis is related to the extent of operation only in patients staged more than T1M0. 2. A delay > 12 months in completion surgery in patients with differentiated thyroid cancer (tumors > 1 cm of diameter) significantly increases the risk of progression of multifocal disease in thyroid remnants.