DTC Patients Research Articles

Effect of postoperative thyrotropin suppression on bone mineral density in postmenopausal women with differentiated thyroid carcinoma

Objective To investigate the effect of postoperative TSH suppression on bone mineral density (BMD) in postmenopausal women with DTC. Methods Postmenopausal women with postoperative DTC underwent thyroid residual ablation or 131I treatment for metastases at Xin Hua Hospital between September 2009 and December 2014 were enrolled and followed for 2 years. They were divided into suppressive TSH group (median TSH<0.30 mU/L; group 1) and non-suppressive group (median TSH≥0.30 mU/L; group 2). Lumber 1-4 BMD levels (T scores) were measured by a dual energy X-ray absorptiometry bone densitometer at baseline, 1 year and 2 years after treatment. All patients had calcium and vitamin D supplementation after TSH suppression. The T scores were compared with Mann-Whitney u test and Kruskal-Wallis test. Results A total of 126 patients were enrolled and followed up for 2 years, including 65 with average age (57.65±6.65) years in group 1 and 61 with average age (56.19±7.17) years in group 2. The T scores in group 1 and group 2 at baseline were -1.70(-2.30, -0.55) and -1.30(-2.10, -0.30)(z=-1.660, P>0.05). The difference of T scores was significant in group 1 at baseline, 1-year follow-up and 2-year follow-up (-2.25(-2.48, -0.83), -1.95(-2.70, -0.60); H=6.244, P 0.05). The T values were different between the 2 groups both in 1-year follow-up and 2-year follow-up (z values: -2.170, -2.160, both P<0.05). Conclusions TSH suppression significantly increases the risk of postoperative osteoporosis. The BMD should be followed up annually in postmenopausal DTC patients. Key words: Thyroid neoplasms; Menopause; Bone density; Thyrotropin

Clinical value of TSH-stimulated thyroglobulin in evaluation of metastasis from differentiated thyroid carcinoma after 131I treatment

Objective To investigate the critical value of TSH-stimulated Tg(sTg) in the diagnosis of metastasis from DTC, and to evaluate the diagnostic value of the ratio of sTg to suppressed Tg (sTg/suppressed Tg). Methods A total of 330 post-operative DTC patients(87 males, 243 females, age range: 12-70 years)who underwent thyroid remnant ablation from August 2008 to December 2014 were retrospectively reviewed. Their serum TgAb levels were normal. The patients were divided into non-metastasis group(147 cases)and metastasis group(183 cases) according to results of ultrasonography, CT and WBS. The difference of sTg between the two groups were compared by Mann-Whitney rank sum test. ROC curve was used to analyze the relationship between sTg, sTg/suppressed Tg ratio and metastasis, the cutoff value was calculated. Results The sTg was significantly different between the non-metastasis group and metastasis group: 1.0 (0.1, 2.0) μg/L vs 36.5 (3.9, 126.7) μg/L; u=-6.642, P<0.05. The AUC for ROC curve in metastasis group was 0.85, and the cutoff value was 2.05 μg/L, with the sensitivity 85.2%, specificity 67.3%, and accuracy 82.3%. While sTg<2.05 μg/L, the AUC of sTg/suppressed Tg ratio was 0.941, and the cutoff value was 4.3, with the sensitivity 93.3%, specificity 88.2%, and accuracy 92.3%. Conclusions The sTg has a specific value for the diagnosis of metastasis from DTC after operation and the cutoff value is 2.05 μg/L in this set of patients. The ratio of sTg/suppressed Tg could be used to correct the sTg and to improve the diagnostic sensitivity. Key words: Thyroid neoplasms; Neoplasm metastasis; Radiotherapy; Iodine radioisotopes; Thyroglobulin

分化型甲状腺癌研究进展

在内分泌恶性肿瘤中，甲状腺癌发病率最高、发病率增长最迅速。每一年的新发例数约占全身所有恶性肿瘤的1.1%，DTC占90%以上，DTC中主要包括85%的乳头状癌和10%的滤泡状癌。DTC患者10年生存率为90%，约10%出现转移，远处转移肺为主、骨次之，骨转移患者10年生存率仅13%~21%，这已成为患者死亡的主要原因。早期诊治尤为重要，现对DTC诊疗新进展简要综述，包括血清甲状腺球蛋白、促甲状腺激素、131I-WBS、18FPET/CT。 In endocrine malignancies, the incidence of thyroid cancer is the highest, and the incidence is the fastest growing. Every year the new number of cases accounted for about 1.1% of all malignant tumors, differentiated thyroid carcinoma accounted for more than 90%, consists of 85% papillary carcinomas and 10% papillary carcinoma. DTC patients with 10 year survival rate was 90%, about 10% had metastases. Metastasis of lung was mainly located in the distance, and bone took the second place. The 10 year survival rate of bone metastasis was only 13%~21%, which has become the main reason for the death of patients. Early diagnosis is particularly important, the new progress of DTC diagnosis and treatment are briefly reviewed, including serum thyroglobulin, thyroid stimulating hormone, 131I-Whole Body Scan, 18Fluorodeoxyglucose-Positron Emission Computerized Tomography/ Computed Tomography.

Serial stimulated thyroglobulin measurements are more specific for detecting distant metastatic differentiated thyroid cancer before radioiodine therapy

ObjectivePreablative stimulated thyroglobulin (ps-Tg) has the potential to be used in identifying distant metastatic differentiated thyroid carcinoma (DM-DTC), but its single level can be affected by remnant thyroid tissue and thyrotropin (TSH). The objective of this retrospective study was to evaluate the value of serial ps-Tg measurements in identifying DM-DTC specifically.MethodsA total of 317 DTC patients with serial measurements of ps-Tg, TSH and anti-Tg antibody were divided into M1 (n=72) and M0 (n=245) according to the presence of distant metastasis (DM) or not. The initial ps-Tg measurement, with a corresponding TSH exceeding 30 μIU/mL, was marked as Tg1, and ps-Tg measured right before radioactive iodine (RAI) therapy was defined as Tg2, with a median interval of 8 days. ΔTg denotes Tg2–Tg1, and ΔTSH denotes TSH2–TSH1. Tg1, Tg2, ΔTg, and ΔTg/ΔTSH were tested for efficacy in identifying DM-DTC using receiver operating characteristic (ROC) curve analysis, and further compared with chest computed tomography (CT) and posttreatment whole-body RAI scan (RxWBS).ResultsCompared with single ps-Tg measurement (Tg1 or Tg2), both ΔTg and ΔTg/ΔTSH were more narrowly distributed around zero in the M0 group, which made their distribution in the M1 group more distinguished in a relatively dispersed way. ΔTg/ΔTSH manifested a higher accuracy (88.64%) and specificity (90.20%) in identifying DM-DTC than Tg1 or Tg2 measurements, with a much higher specificity than chest CT (90.20% vs. 66.00%) and a much higher sensitivity than RxWBS (83.33% vs. 61.11%). ConclusionsSerial ps-Tg measurements even over as short an interval as 8 days hold incremental value in identifying DM-DTC. ΔTg/ΔTSH is a specific early biochemical marker for DM-DTC.

Nodular thyroid disease in the elderly: novel molecular approaches for the diagnosis of malignancy.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60year, and 60% in men older than 80year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

Change of pre-ablative thyroid-stimulating hormone after thyroid hormone withdrawal and its response to 131I therapy in patients with low to intermediate risk differentiated thyroid cancer

Objective To investigate the relationship between the change of pre-ablative TSH after thyroid hormone withdrawal(THW) and the response of subsequent 131I therapy in patients with low to intermediate risk DTC after total or near total thyroidectomy. Methods A total of 120 DTC patients (38 males, 82 females, age (40.8±10.9) years) were enrolled in this retrospective study. Serial TSH levels determined on the day of THW and on the day of receiving 131I ablative therapy were monitored, which were marked as TSH1 and TSH2 accordingly. The THW duration (t) was recorded, the change of TSH was defined as ΔTSH and the change rate of TSH was calculated (V=ΔTSH/t). The responses to 131I therapy were classified as excellent response(ER), indeterminate response (IDR), biochemical incomplete response (BIR) and structural incomplete response (SIR) according to ATA guideline. According to the TSH2 (mU/L) levels, patients were divided into G1 group (30≤TSH2 5.0) , and their responses to 131I ablation were compared. Patients were classified into R1 group (including ER and IDR) and R2 group (including BIR and SIR), the differences of clinical and pathological features, 131I doses between the two groups were explored. Furthermore, logistic regression was performed to identify factors associated with BIR and SIR. Results Patients with male gender (χ2=11.863), younger age(F=4.975), and faster TSH change rate (H=44.911) and lower thyroid residue (H=18.159) achieved a higher value of TSH2 (all P 0.05). TSH2 level(OR=0.835) and pre-ablative Tg level (OR=1.196) were independent factors in predicting BIR and SIR (both P<0.05). Conclusions The changing rate of TSH before 131I ablation may not be associated with the response to 131I therapy in patient with low to intermediate risk DTC, while the level of TSH2 does. Patients with TSH2 ranging from 90 to 120 mU/L could be of help in achieving a better clinical response. Key words: Thyroid neoplasms; Thyrotropin; Radiotherapy; Iodine radioisotopes; Treatment outcome

Evaluating the influence of prophylactic central neck dissection on TNM staging and the recurrence risk stratification of cN0 differentiated thyroid carcinoma

The purpose of this study was to explore the risk factors that were associated with central lymph node metastasis (CLNM) in patients with clinical nodal negative differentiated thyroid carcinoma (cN0 DTC) after prophylactic central neck dissection (pCND). The influence of pCND on TNM staging and recurrence risk stratification (RRS) in patients with cN0 DTC was also evaluated in our study. A total of 153cN0 DTC patients in Guangdong general hospital who underwent thyroidectomy with pCND from March2014 to October2014 were enrolled in this study. The relations of CLNM with clinicopathologic characteristics of cN0 DTC were analyzed by univariate and multivariate logistic regression. The influence of pCND on migration of TNM staging and RRS in cN0 DTC was observed. In the present study, CLNM was found in 42.5% (65 of 153cases) of patients with cN0 DTC. On univariate analysis, the age less than 45years old, tumor size more than 2cm, pT staging, and a total number of central lymph nodes dissected more than 3 were significantly associated with CLNM (P<0.05); however, gender, tumors affecting both lobes, multifocality, capsular invasion, and Hashimoto's thyroiditis were not related with CLNM (P>0.05). On multivariate logistic regression, age<45years (P=0.001) and a total number of central lymph nodes dissected >3(P=0.002) were significantly associated with CLNM. Because of the identification of CLNM in the implementation of pCND, 15 (9.8%) of 153cN0 DTC patients were upgraded in TNM staging; all these patients were older than 45years. Fifty-six patients (36.6%) developed higher RRS (from low to intermediate) after pCND. For younger patients (age<45years), careful preoperative assessment of the lymph node status must be done; surgeons should consider this risk factor when deciding whether to perform pCND. Thorough lymphadenectomy in the implementation of pCND can avoid residual lymph node metastasis and help to increase the incidence of CLNM. pCND can indentify occult CLNM which allows more precise TNM staging (for patients with age≥45years) and RRS.

Metastatic malignant struma ovarii with coexistence of Hashimoto's thyroiditis.

SummaryStruma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii) has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with 131I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients.Learning pointsMalignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined.Predominant sites of metastasis are adjacent pelvic structures.Thyroidectomy and 131I therapy should be considered after risk stratification in accordance with standard approaches in DTC patients.

Ongoing risk stratification for differentiated thyroid cancer (DTC) - stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients.

Adequate postoperative risk assessment currently constitutes the principle of DTC treatment and further management. The aim of the study - a retrospective assessment of risk factors influencing DTC relapse. The study group consisted of 510 DTC staged pT1b-T4N0-N1M0, in whom total thyroidectomy and complementary radioiodine (RAI) treatment were carried out. In 71% papillary thyroid cancer was diagnosed, whereas in the remaining 29% - follicular thyroid carcinoma. Based on TNM classification from 1997, T1 feature was diagnosed in 11.6%, T2 in 35.1%, T3 in 8.4%, T4 in 9,4%, while in 35.5% - Tx. Lymph node metastases were present in 24.7% of cases. Median follow-up was 12.1 years (1.5-15.2). Age at DTC diagnosis, tumour diameter (T), lymph node metastases (N1), stimulated thyroglobulin, and RAI uptake in thyroid bed at qualification for RAI ablation significantly influenced freedom from progression time (FFP) in a multivariate analysis. When postoperative stimulated Tg was > 30 ng/mL the risk of relapse increased nearly six-fold, whereas the presence of N1 feature - four-fold. The total risk of relapse in the whole group was 12.55% while median FFP was 154.8 months. Five-year and 10-year FFP was 90.1% and 87.5%, respectively. Postoperative stimulated thyroglobulin level was the most potent, independent risk factor influencing FFP in DTC patients. Age above 60 years, an initial DTC stage (T and N features), and low RAI uptake in thyroid bed ( < 1%) were related to a higher risk of DTC relapse, whereas the investigated histopathological features were insignificant.

Radioactive Iodine Administration Is Associated with Persistent Related Symptoms in Patients with Differentiated Thyroid Cancer.

Context. Radioiodine (RAI) administration has adverse effects in patients treated for thyroid cancer (DTC), but there is scarce information regarding their intensity and duration. Objective. To evaluate frequency and intensity of early and late RAI-related symptoms in patients with DTC. Design. Observational prospective study. Patients. DTC patients who underwent thyroidectomy, with or without RAI. Measurements. Patients answered 2 surveys: (1) from 0 to 6 months and (2) between 6 and 18 months after initial treatment. Results. 110 patients answered the first survey and 61 both. Nearly 80 percent received RAI. Among early symptoms, periorbital edema, excessive tearing, salivary gland disturbances, dry mouth, taste disorders, and nausea were more frequent and intense among RAI patients. Regarding late symptoms, periorbital edema, salivary gland pain and swelling, and dry mouth were more frequent and intense in RAI patients. Frequency and intensity of adverse effects were not different between low and high RAI doses (50 versus ≥100 mCi). Conclusion. RAI-related symptoms are frequent and usually persist after 6 months of administration, even when low doses are given. This finding must be considered when deciding RAI administration, especially in low risk patients, among whom RAI benefit is controversial.

Influencing factors on the function of sodium iodide symporter in differentiated thyroid cancer

The expression and function of NIS are the prerequisites of radioactive iodine(RAI) treatment for DTC, which in turn determine the iodine uptake and outcome in DTC patients. Studies for the factors that might influence the function of NIS for the development of redifferentiation therapy should be conducted in conjunction with the individualized course of treatment in DTC patients having poor iodine uptake in their thyroid tumors. This review summarizes the factors that influence the function and expression of NIS in these patients. Key words: Thyroid neoplasms; Sodium/iodine symporter; Radiotherapy; Trends

Clinical value of 99Tcm-MIBI scintigraphy in patients with differentiated thyroid carcinoma after surgery and first 131I therapy

Objective To evaluate the clinical value of 99Tcm-MIBI scintigraphy for diagnosis of residual thyroid tissue and metastasis in patients with DTC after their first 131I therapy. Methods From February 2010 to March 2014, 192 DTC patients (38 males, 154 females, average age (43.2±8.6) years) who received total or near-total thyroidectomy and were pathologically diagnosed as DTC (171 papillary and 21 follicular carcinomas) underwent 99Tcm-MIBI scan (average dosage: 740-925 MBq) 6 months after their first 131I therapy. 131I scans was performed 4 d after oral administration of 131I of therapeutic dose (average dosage: 5 550-8 140 MBq). Pre- and post-therapeutic images and the serum Tg level (detected before the imagings) were compared and analyzed. Any abnormal uptake of agent found inside or outside the thyroid was regarded as positive result. Patient-based and lesion-based data analysis were performed by χ2 test and two-sample t test. Results A total of 191 patients were finally included, of which 65 positive cases were found. The sensitivity of 99Tcm-MIBI imaging was significantly lower than that of 131I imaging(56.9% (37/65) vs 92.3%(60/65); χ2=14.7, P 0.05). The serum Tg level of positive groups (99Tcm-MIBI positive + 131I positive or 131I negative) were significantly higher than that of 99Tcm-MIBI negative + 131I negative group (t=-20.7 and -6.0, both P<0.01), and that of 99Tcm-MIBI positive + 131I negative group was higher than that of 131I positive + 99Tcm-MIBI negative group(t=-2.7, P<0.05). Conclusion 99Tcm-MIBI imaging could detect metastasis of DTC patient after first radioiodine therapy, but the value in detecting thyroid remnants is limited. Key words: Thyroid neoplasms; Radiotherapy; Iodine radioisotopes; Radionuclide imaging; MIBI

The influence of distant metastases on serum TSH elevation after L-T4 withdrawal in differentiated thyroid cancer

Objective To investigate the influence of distant metastases on the increase rate (vx) of serum TSH and its change rate(Ra) in patients with DTC after thyroid hormone withdrawal (THW). Methods Three times or more serum TSH measurements were performed before and after THW in 97 patients (38 males, 59 females) who had underwent successful 131I ablation from January 2014 to July 2014. v1 (early period vx), v2 (later period vx) and change rate of v1 and v2 (Ra) were calculated and compared between M0 group (without distant metastases, n=67) and M1 group (with distant metastases, n=30). Two-sample t test and rank-sum test were used for statistical analysis. Results v1 in males was significantly higher than that in females ((3.58±2.13) vs (2.63±1.54) mU·L-1·d-1; t=2.549, P=0.012). v2 in M0 group was significantly higher than that in M1 group ((7.67±3.66) vs (3.68±4.33) mU·L-1·d-1; t=3.613, P=0.001). The difference of Ra between M0 group and M1 group was statistically significant(z=-4.17, P<0.05). Conclusions Distant metastases may affect the increase rate and its change pattern of serum TSH after THW. Serum TSH showed a slow elevation over time or even decline in patients with distant metastasis. Meanwhile TSH increased much higher over the THW time in most of the patients in M0 group. It was suggested that attention should be paid to the variation of serum TSH in DTC patients with distant metastases to avoid decrease of TSH during longer THW. Key words: Thyroid neoplasms; Neoplasm metastasis; Surgery, operative; Radiotherapy; Iodine radioisotopes; Thyroxine; Thyrotropin

Familial Non-Medullary Thyroid Cancer Represents an Independent Risk Factor for Increased Cancer Aggressiveness: A Retrospective Analysis of 74 Families

To assess whether familial non-medullary thyroid cancer (FNMTC) represents an independent risk factor for increased aggressiveness of the tumor, as concern as the clinical presentation and the long-term follow-up in respect of sporadic differentiated thyroid cancer (SDTC). Retrospective study; 1976-2014. Seventy-four FNMTC families (151 affected individuals): family relationship and number of affected family members were evaluated. Clinical and histopathological features and outcome were compared to that of 643 SDTC patients followed in the same period according to the same institutional protocols. Median follow-up was 57.7 months (range 12-136) in FNMTC and 59.7 (range 15-94.6) in SDTC patients. Three cases occurred in 3 families and 2 cases in the other 71. F:M was 3.7:1 in FNMTC and 4.3:1 in SDTC (NS). The family relationship was siblings in 62.2%. Mean age at diagnosis was lower in FNMTC than in SDTC (p < 0.005). Papillary/follicular histotype distribution was similar (86%). Papillary tumors were more frequently multifocal in FNMTC (p = 0.004) and with lymph-node metastases (p = 0.016). Disease-free survival (DFS) was shorter in FNMTC vs. SDTC (p < 0.0001) with 74.8 vs. 90.8% patients free of disease at the last control (p < 0.005). Three patients died in FNMTC group vs. 1 in SDTC (p = 0.02). Familial non-medullary thyroid cancer displays distinct characteristics as earlier age of onset and increased aggressiveness at diagnosis and a higher rate of persistent/recurrent disease and mortality with a shorter DFS in respect with SDTC. FNMTC patients, therefore, should be followed accurately. As the specific gene (or genes) responsible for susceptibility for FNMTC has not yet been identified, a low frequency periodic screening of relatives DTC patients may be useful to identify FNMTC patients at early stage of disease.

Values of serum midkine in diagnosis and prognosis prediction of differentiated thyroid cancer

Objective To investigate values of serum midkine (MK) as a diagnostic biomarker in DTC before surgery, and as a prognostic biomarker before 131I ablation therapy. Methods A total of 162 patients (70 patients with DTC and 92 patients with benign thyroid nodules) participated in the surgical cohort, 75 healthy subjects served as controls. Diagnostic values of pre-surgical MK and Tg for DTC were conducted by ROC curves. A total of 214 DTC patients participated in the 131I treatment cohort. Prognostic values of pre-131I-ablative MK and Tg to predict 131I-avid metastases were performed by ROC curves. Independent two-sample t test or Mann-Whitney u test was used to analyze the data. The relationship between MK and Tg was analyzed by Pearson correlation analysis. Metastasis-free survival was analyzed by Kaplan-Meier method. Results MK and Tg were positively correlated (r=0.917, P<0.05). Pre-surgical MK and Tg levels were significantly higher in DTC patients than those in benign thyroid nodule patients (z=-7.283 and-3.191, both P<0.05) and those in controls (z=-7.328 and-4.384, both P<0.05). The best cut-off value of MK for differentiating DTC from benign thyroid nodules was 323.12 ng/L and the diagnostic accuracy was 75.31% (122/162), which was better than the diagnostic accuracy of Tg (60.49%, 98/162). Pre-131I-ablative Tg demonstrated perfect ability to predict metastases, with cut-off value of 19.50 μg/L and diagnostic accuracy of 96.73%(207/214). MK also performed well with cut-off value of 504.71 ng/L and diagnostic accuracy of 89.25%(191/214). DTC patients with MK or Tg levels higher than thresholds (500 ng/L, 20 μg/L) showed a significantly worse 131I-avid metastasis-free survival by Kaplan-Meier analysis (χ2=118.539 and 209.823, both P<0.05). Conclusions MK can not only be used to screen DTC patients, but also be used to predict metastases before 131I ablative therapy. It is suitable to serve as a serum biomarker for DTC. Key words: Thyroid neoplasms; Cytokines; Thyroglobulin; Diagnosis, differential

Not all DTC patients with N positive disease deserve the attribution "high risk". Contribution of the MSDS trial.

To investigate if patients with thyroid carcinoma having N1a disease are at the same risk with N1b using the collective of the well-defined European prospective Multicentre Study Differentiated Thyroid Cancer (MSDS). Overall (OS) and event free survival (EFS) were calculated. Cox multivariable regression analysis was performed in order to calculate Hazard ratios (HR). EFS was significantly decreased only in patients with N1b metastasis as compared to N0 patients and became worse when N1a was concomitantly affected. A superior survival in favor of N1a patients as compared to N1b patients with regard to EFS was also observed. The patients having N1a disease showed no differences in the EFS as compared to N0. OS did not differ significantly in any of the groups. There was an increased HR for events with regards to histology, T-stage, tumor size, UICC stage and cervical lymph node metastasis. Tumor size showed a significantly increased risk for OS. Patients with pT3b and pT4a tumors with N1b are of higher risk for relapse, albeit not affecting overall survival. Patients with N1a are of no higher risk. The risk stratification of these patients may be adapted accordingly.

Intermediate-risk differentiated thyroid carcinoma patients who were surgically ablated do not need adjuvant radioiodine therapy: long-term outcome study.

The mute question is whether patients with DTC of intermediate risk of recurrence, second most common presentation, who were surgically ablated in the first place, ever needed adjuvant RAI therapy? This study exclusively evaluated the long-term outcome in intermediate-risk patients with DTC. Two-arm retrospective cohort study conducted between years 1991 and 2012. Institutional practice. Intermediate-risk DTC patients, with pathologically proven T1/2N1M0, T3 with/without N1 M0 disease, with a minimum follow-up of 12months, were included. Of 254 patients who fulfilled the inclusion/exclusion criteria, 125 patients were surgically ablated (Gr-I) and 129 patients had significant remnant and/nodal disease (Gr-II). No radioiodine in Gr-I and adjuvant RAI therapy was administered in Gr-II patients. Baseline characteristics were compared and overall survival, event-free survival, disease-free survival/overall remission rates and recurrence rates were calculated for both the groups. All baseline patient characteristics were comparable except 24-h RAIU between two groups. Depending on adjuvant radioiodine therapy outcome, Gr-II patients were subclassified as Gr-IIa (ablated) and Gr-IIb (not ablated). With a median follow-up duration of 10·3years (range: 1-21years), 12/125 (9·6%) patients had disease recurrence and 10 (8%) showed persistent disease in Gr-I. In Gr-IIa, 6/102 (5·9%) patients recurred but only one of them was successfully ablated with (131) I, and 5 (4·9%) had persistent disease. However, in Gr-IIb, 27 patients who failed first-dose adjuvant RAI therapy, 8/27 (29·6%) showed persistent disease (P=0·000). Overall survival was 100%; however, disease-free survival rates were 92% and 90%, in Gr-I and Gr-II, respectively. Intermediate-risk surgically ablated patients do not need adjuvant RAI therapy and patients who failed to achieve ablation with first dose of (131) I may be dynamically risk stratified as high-risk category and managed aggressively.

Dynamic change of peripheral blood cell in patients with differentiated thyroid cancer before and after 131I treatment

Objective To evaluate the kinetics of peripheral blood cells in DTC patients before and after 131I treatment. Methods A total of 64 patients were divided into 2 groups with different therapeutic doses: high-dose group (3.70-5.55 GBq, n=24) and low-dose group (1.11 GBq, n=40). The WBC, neutrophils (NEUT), lymphocytes (LY), RBC and PLT were counted before operation, before 131I treatment, and on 3 d and 7 d after 131I treatment. One-way analysis of variance and two-sample t test were used to analyze the data. Results The counts of WBC and NEUT in both groups along with the LY in high-dose group varied significantly before, and on 3 d and 7 d after 131I treatment(WBC: high-dose group,(6.30±1.04),(8.86±2.07),(6.59±1.64) ×109/L; low-dose group,(6.65±1.48),(10.17±3.04),(7.17±1.57)×109/L; NEUT: high-dose group,(3.75±0.88),(6.42±1.91),(4.53±1.54)×109/L; low-dose group,(3.88±0.90),(7.12±2.77),(4.40±1.17)×109/L; LY: (2.11±0.67),(2.06±0.74),(1.59±0.49)×109/L;F values: 3.88 to 30.20, all P<0.05). The counts of WBC and NEUT in both groups were significantly higher on 3 d after 131I treatment than that before treatment (all P<0.05). The counts of WBC and NEUT in both groups along with the LY in high-dose group decreased significantly on 7 d compared to that on 3 d after 131I treatment (all P<0.05). The counts of LY in high-dose group also significantly decreased on 7 d after 131I treatment than before treatment(P<0.05). The counts of RBC before 131I treatment and LY on 7 d after 131I treatment were significantly different between the 2 groups(t=2.36, -4.30, both P<0.05). Compared with the counts before operation, LY, RBC and PLT were significantly higher (t values: from-4.92 to-2.45, all P<0.05) during hypothyroid state induced by thyroxine withdrawal before 131I treatment. Conclusions Short-term kinetics of WBC and NEUT present as an increase first followed by a decrease after 131I treatment; while LY of high-dose group presents as a gradually decrease. Hypothyroid state induced by levo-thyroxine withdrawal leads to increased counts of LY, RBC and PLT before 131I treatment. Key words: Thyroid neoplasms; Radiotherapy; Iodine radioisotopes; Blood cells

VEGF-D and A Preoperative Serum Levels Predict Nodal and Distant Metastases in Differentiated Thyroid Cancer Patients.

Preoperative tumor aggressiveness biomarkers may help surgeons decide the extent of an operation. However, whether serum angiogenetic factors can be used to predict the prognosis of patients with differentiated thyroid cancer is still unclear. Seventy-six DTC patients were prospectively recruited. Preoperative serum samples were collected and measured for Tie-2, Ang-1, Ang-2, VEGF-A, and VEGF-D levels. The potential correlations between their serum levels and clinicopathologic features as well as their prognoses were analyzed. Older age (>45 years old) and higher VEGF-A serum levels were independent predictors of extrathyroidal extension. The VEGF-D serum level was an independent factor for lymph node metastases and VEGF-A was an independent factor for distant metastases. None of these serum angiogenetic factors were significantly different between patients who were disease free and those with recurrences. The presence of lymph node metastases was the only independent factor for recurrence over the 2-year follow-up. Preoperative serum VEGF-A and VEGF-D levels were significantly elevated in DTC patients with distant and lymph node metastases. These findings, when combined with other clinicopathological factors, may help in surgical decisions.

Patient Benefit-Risk Tradeoffs for Radioactive Iodine-Refractory Differentiated Thyroid Cancer Treatments.

Background. The aims of this study were to assess patients' preferences to wait or start systemic treatment and understand how patients would make tradeoffs between certain severe adverse events (AEs) and additional months of progression-free survival (PFS). Materials and Methods. Adults in France, Germany, and Spain with a diagnosis of DTC and who have had at least one RAI treatment completed a direct-elicitation question and a discrete-choice experiment (DCE) online. The direct-elicitation question asked respondents whether they would opt out of treatment when their tumor is RAI-R. In the DCE, respondents chose between 12 pairs of hypothetical RAI-R DTC treatment profiles. Profiles were defined by magnitudes of efficacy (PFS) and safety (severe hand-foot skin reaction [HFSR], severe proteinuria, and severe hypertension). A main-effects random-parameters logit model was estimated. Results. 134 patients completed the survey. Most patients (86.6%) opted for treatment rather than “wait and see” decision. Patients placed a greater weight on the risk of severe hypertension than the risk of proteinuria and HFSR. Conclusions. DTC patients showed preference toward treatment for RAI-R DTC over watchful waiting. Patients' concerns about the risk of severe hypertension appeared to have had a greater effect on patients' choice than severe proteinuria or HFSR.